Diabetic osteoporosis (DOP) is a metabolic bone disease characterized by abnormal bone tissue structure and reduced bone strength in patients with diabetes. Its pathogenesis is complex, involving multiple factors rather than a single cause, and has not yet been fully elucidated. Cuproptosis, a novel form of programmed cell death discovered in 2022, differs mechanistically from apoptosis, necroptosis, and ferroptosis. This process relies on the accumulation of intracellular copper ions and is closely associated with mitochondrial respiration. Studies have indicated that cuproptosis is intimately linked to glucose metabolism and bone metabolism. This review explores the role of copper homeostasis in maintaining glucose metabolism and bone quality and systematically elucidates the potential associations between cuproptosis and these processes from molecular, cellular, and pathophysiological perspectives, aiming to provide new insights and prospects for future research directions in diabetic osteoporosis.

ETHNOPHARMACOLOGICAL RELEVANCE:Knee osteoarthritis (KOA) is a prevalent degenerative joint disease with limited effective treatments. Synovial mesenchymal stem cells (SMSCs) are recognized for their superior potential in cartilage regeneration compared to other stem cells. Duhuo Jisheng Decoction (DHJSD), is a traditional Chinese formulation used for centuries to treat KOA. While most studies on DHJSD have focused on chondrocytes, its effects on SMSCs or exosome derived from SMSCs have not been explored. AIM OF THE STUDY:This study aims to investigates the therapeutic effects of DHJSD on repairing cartilage via SMSCs-derived exosomes mediating the microRNA (miR)-194-5p/Wnt Signaling Pathway. MATERIALS AND METHODS:Extracts of DHJSD were prepared from single batch of formulations, and LC-MS was used to analyze the components. KOA rat model with bilateral anterior cruciate ligament transection, primary SMSCs and H2O2-induced chondrocytes were established and treated with DHJSD. H&E, toluidine blue, and safranin O/fast green staining was used to assess the cartilage injury and repair, TUNEL staining was used to evaluate the level of apoptosis. Exosomes derived from DHJSD-pretreated SMSCs (DHJSD-Exo) were collected and identified by transmission electron microscopy and nanoparticle tracking analysis. The exosomal miRNA profile was analyzed through RNA sequencing and quantitative polymerase chain reaction (qPCR), and chondrocytes were intervened with 100 nM miRNA mimic/inhibitor and different doses of DHJSD-Exo. Single-cell RNA sequencing analysis was utilized to classify chondrocyte subpopulations. Additionally, chondrocyte differentiation and apoptosis following treatment with DHJSD-Exo (10 μg/mL) or the Wnt agonist BML-284 (10 μM) were investigated using Western blotting, qPCR toluidine blue staining, crystal violet staining and flow cytometry. RESULTS:DHJSD significantly mitigates cartilage destruction and reduces the extracellular matrix degradation and inhibits apoptosis in KOA rats. Also, DHJSD promotes SMSCs proliferation, and enhances chondrogenic differentiation. Additionally, DHJSD modulated the miRNA profile in exosomes derived from serum and DHJSD-pretreated SMSCs (DHJSD-Exo), with DHJSD-Exo further promoting chondrogenic differentiation in H2O2-induced chondrocytes. Single-cell RNA sequencing results indicated that the Proc sub-cluster of chondrocytes is responsible for cartilage repair and regeneration. Gene Set Enrichment Analysis (GSEA) results indicated that endocytosis and the Wnt signaling pathway are involved in the process of cartilage remodeling. Notably, inhibition of miR-194-5p targets the Wnt3a/β-catenin signaling pathway, suppressing chondrogenic differentiation and promoting apoptosis in H2O2-induced chondrocytes, while DHJSD-Exo reverses there effect. Overexpression of miR-194-5p exhibited the opposite effects, and the pro-chondrogenic effects of DHJSD-Exo via the Wnt signaling pathway could be blocked by BML-284, a Wnt signaling inhibitor. CONCLUSION:DHJSD not only enhances SMSCs proliferation and chondrogenic differentiation, but also stimulates chondrocyte activity via DHJSD-Exo mediated activation of the miR-194-5p/Wnt signaling pathway, offering promising insights into KOA treatment. Future research should focus on advancing these promising insights toward clinical application, through further mechanistic exploration, translational studies, and ensuring the consistency of the multi-herbal formula.

Drynariae Rhizoma has been commonly used as a preventive and therapeutic agent for bone diseases. However, its pharmacological mechanisms have not been fully elucidated. Here, we aimed to investigate the effects of Drynariae Rhizoma in a bilateral ovariectomized rat model and explore the correlation with gut microbiome. We established an ovariectomized rat model, which we treated with different doses of Drynariae Rhizoma (Drynariae Rhizoma-Low, 0.27 g/kg/day; Drynariae Rhizoma-Middle, 0.81 g/kg/day; Drynariae Rhizoma-High, 2.43 g/kg/day) through intragastric administration for 12 weeks. Results showed that Drynariae Rhizoma alleviated body weight, moderated bone microstructure, and promoted the expression of bone formation-related factors in ovariectomized rats, in which Drynariae Rhizoma-High showed the most significant effects among the three doses. Furthermore, the effects of Drynariae Rhizoma on promoting bone formation were correlated to the changes in microbial richness and the restorations of several genera, among which Ruminiclostridium and Ruminococcaceae_UCG_007 were positively correlated with the bone formation-related factors, and both were enriched in the Drynariae Rhizoma-High group as biomarkers. Moreover, CMP-legionaminate biosynthesis I might be a crucial pathway of Drynariae Rhizoma to regulate gut microbiota. The content of serum short-chain fatty acids in the ovariectomized rats were regulated by Drynariae Rhizoma. Our results demonstrate that Drynariae Rhizoma promotes bone formation in ovariectomized rats, and is related to the regulation of the gut microbiota structure.

Osteoporosis (OP) is characterized by impaired bone formation, largely attributed to dysfunctional osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Circulating factors, particularly exosomes acting as natural nanocarriers, play crucial roles in regulating BMSCs function within the bone microenvironment. However, the specific mechanisms by which serum exosomes contribute to osteogenic impairment in OP remain elusive. Serum exosomes were isolated from ovariectomized (OVX) rats and characterized. Their impact on BMSCs osteogenesis was evaluated. Global miRNA sequencing identified dysregulated miRNAs in OVX-derived exosomes. The roles of miR-29a-3p and miR-29c-3p were investigated using gain- and loss-of-function approaches in vitro and in vivo. Bioinformatic analysis and experimental validation identified Ten-Eleven Translocation 3 (TET3) as a direct target. TET3 deficiency was modeled in OVX mice. Transcriptomic analysis, bisulfite sequencing PCR, and chromatin immunoprecipitation sequencing were employed to delineate the mechanism of action of TET3. Exosomes derived from OVX rat serum significantly inhibited osteogenic differentiation of BMSCs. MiRNA sequencing revealed a pronounced downregulation of miR-29a-3p and miR-29c-3p within these exosomes. Functionally, overexpression of miR-29a/29c-3p rescued bone formation defects both in vitro and in vivo, while their inhibition suppressed osteogenesis. Mechanistically, TET3, a key DNA demethylase, was confirmed as a direct target of miR-29a/29c-3p. Crucially, TET3 deficiency in OVX mice stimulated BMSCs osteogenesis and bone remodeling. Further mechanistic dissection demonstrated that TET3 represses osteogenesis by directly increasing DNA methylation at the Sox9 promoter, thereby suppressing Sox9 expression, and concurrently inhibiting the PI3K/AKT signaling pathway. Our study defines a novel exosome-mediated pathway in OP: Deficiency of serum exosome-delivered miR-29a/29c-3p elevates TET3, which epigenetically represses Sox9 via promoter hypermethylation and inhibits PI3K/AKT signaling. This exosome/miR-29/TET3/Sox9 axis unveils promising therapeutic targets for OP intervention, particularly leveraging exosome-based modulation or epigenetic editing.

BACKGROUND:Accumulating evidence shows that Panax notoginseng, a well-known medicinal herb, has an ideal effect on prevention and treatment of skeletal diseases. In this study, we reviewed clinical applications of clinical application as well as phytochemistry, pharmacokinetics, pharmacology in improving bone quality and toxicity of Panax notoginseng. PURPOSE:Review the phytochemistry, pharmacokinetics, pharmacology involved in the improving bone metabolism and toxicity of Panax notoginseng and evaluate its potential as a traditional Chinese herbal medicine for osteoporosis. METHODS:Several databases were consulted, including PubMed, China National Knowledge Infrastructure, National Science and Technology Library and Web of Science. The following words or phrases were used alone or in combinations in the titles and/or abstracts: "","Panax notoginseng", "Sanqi", "osteoporosis", "bone", "osteoblast", "osteoclast", "phytochemistry", "pharmacology" and "pharmacokinetics". Altogether 160 papers were cited. RESULTS:8 clinical trials of Panax notoginseng alone for the treatment of osteoporosis were identified, most of which used traditional Chinese patent medicines to treat osteoporosis fractures. In these clinical trials, Panax notoginseng preparations have achieved relatively good therapeutic effects. However, more rigorous large-scale experiments are expected to prove their efficacy. Phytochemistry study showed that saponins, flavonoids, polysaccharides are the main active ingredients extracted from Panax notoginseng and the transformation of saponins during the processing explains the different effects of raw and cooked Panax notoginseng. The pharmacokinetics data reveals that protopanaxdiol-type (ppd-type) saponins possesses higher bioavailability than protopanaxtriol-type(ppt-type) saponins and ppd-type saponins such as ginsenoside Ra3, Rb1, and Rd can represent suitable pharmacokinetic markers for Panax notoginseng extracts. The data from animal experiments demonstrates that Panax notoginseng can improve bone quality in ovariectomized, diabetic, hyperlipidemia, radiation-induced, and arthritis rats through the regulation of anti-adipogenesis, anti-inflammation, anti-oxidation, angiogenesis and estrogenic effects. In vitro experiments, the activities of improving bone quality of Panax notoginseng and its ingredients may be attributed to the regulation of multiple signaling pathways, including Wnt/β-catenin, BMP/BMP-R, AMPK/mTOR, GPER/PI3K/AKT, etc. Acute and chronic toxicity as well as genotoxicity studies show that Panax notoginseng is well tolerated while long term use may lead to liver and kidney toxicity. CONCLUSIONS:Panax notoginseng is a superior medicinal herb that contains multiple active ingredients and could play a potential role in the prevention and treatment of osteoporosis. Further studies should concentrate on developing Panax notoginseng products with higher curative effect and bioavailability.

Osteoporosis (OP) is a complex bone metabolism disorder disease that affects the skeleton, nervous system, muscles, and multiple tissues. Neuropeptides, which are endogenous substances derived from both bone and brain, play a critical role in maintaining the balance of bone metabolism. This review summarizes research conducted from 1986 to 2024 on the pathological mechanisms of neuropeptides and their receptors in the context of OP. Specifically, the roles of Neuropeptide Y, Vasoactive Intestinal Peptide, Calcitonin Gene-Related Peptide, and Substance P and their receptors in key processes of OP were examined, including their function of bone formation and resorption, osteoblast differentiation, and osteoclast differentiation. Our study showed that these neuropeptides could promote bone formation and inhibit bone resorption, while their receptors in osteocytes exhibit distinct functions, indicating complex regulatory mechanisms that require further investigation. Additionally, we summarize the progress of Traditional Chinese Medicine (TCM) formulae, single TCM herbs, and bioactive compounds derived from TCM in exerting anti-OP effects through neuropeptide modulation. These studies highlight the multi-targeted and multi-mechanistic pharmacological actions of TCM in treating OP. By integrating these findings, we aim to enhance the understanding of neuropeptides’ roles in bone metabolism and to explore the development of neuropeptide-targeted TCM therapies for OP management. This comprehensive perspective highlights the potential of neuropeptides as therapeutic targets, paving the way for innovative approaches to treating OP.

Postmenopausal osteoporosis, primarily driven by estrogen deficiency, is predominantly mediated through estrogen receptors such as ER alpha. However, the underlying mechanisms necessitate further investigation. In this study, we established an ER alpha-deficient model in rBMSCs to elucidate the role of ER alpha in osteogenic differentiation and miRNA expression profiles. Our findings demonstrate that knockdown of ER alpha inhibits osteogenic differentiation in rBMSCs, resulting in upregulation of 25 miRNAs and downregulation of 184 miRNAs, including a significant increase in the expression of miR-214-3p. Validation using qPCR, Western blotting, and bioinformatics analysis revealed that miR-214-3p negatively regulates osteogenic differentiation via the Wnt/beta-catenin signaling pathway. Furthermore, we explored the potential therapeutic effects of quercetin (QUE) on rBMSCs. CCK8, alkaline phosphatase activity assays, and Alizarin Red staining demonstrated that QUE dose-dependently enhances rBMSCs proliferation, alkaline phosphatase activity, and mineralization within the concentration range of 0.1-1 mu M. Importantly, QUE was found to downregulate miR-214-3p expression and activate the Wnt3a/ beta-catenin signaling pathway. Rescue experiments confirmed that QUE could counteract the inhibitory effects of miR-214-3p on the Wnt3a/beta-catenin signaling pathway. Collectively, our study provides compelling evidence that knockdown of ER alpha inhibits the osteogenic differentiation of rBMSCs by affecting the miRNA expression profile, while QUE can reverse the inhibitory effect exerted by miR-214-3p on the Wnt3a/beta-catenin signaling pathway, thereby offering novel insights into diagnosis, prevention, and treatment strategies for postmenopausal osteoporosis.

To investigate the Wnt signaling pathway and miRNAs mechanism of extracts of Plastrum Testudinis (PT) in the treatment of osteoporosis (OP). Thirty female Sprague Dawley rats were randomly divided into 5 groups by random number table method, including sham group, ovariectomized group (OVX), ovariectomized groups treated with high-, medium-, and low-dose PT (160, 80, 40 mg/kg per day, respectively), with 6 rats in each group. Except for the sham group, the other rats underwent bilateral ovariectomy to simulate OP and received PT by oral gavage for 10 consecutive weeks. After treatment, bone mineral density was measured by dual-energy X-ray absorptiometry; bone microstructure was analyzed by micro-computed tomography and hematoxylin and eosin staining; and the expressions of osteogenic differentiation-related factors were detected by immunochemistry, Western blot, and quantitative polymerase chain reaction. In addition, Dickkopf-1 (Dkk-1) was used to inhibit the Wnt signaling pathway in bone marrow mesenchymal stem cells (BMSCs) and miRNA overexpression was used to evaluate the effect of miR-214 on the osteogenic differentiation of BMSCs. Subsequently, PT extract was used to rescue the effects of Dkk-1 and miR-214, and its impacts on the osteogenic differentiation-related factors of BMSCs were evaluated. PT-M and PT-L significantly reduced the weight gain in OVX rats (P<0.05). PT also regulated the bone mass and bone microarchitecture of the femur in OVX rats, and increased the expressions of bone formation-related factors including alkaline phosphatase, bone morphogenetic protein type 2, collagen type I alpha 1, and runt-related transcription factor 2 when compared with the OVX group (P<0.05 or P<0.01). Meanwhile, different doses of PT significantly rescued the inhibition of Wnt signaling pathway-related factors in OVX rats, and increased the mRNA or protein expressions of Wnt3a, β-catenin, glycogen synthase kinase-3β, and low-density lipoprotein receptor-related protein 5 (P<0.05 or P<0.01). PT stimulated the osteogenic differentiation of BMSCs inhibited by Dkk-1 and activated the Wnt signaling pathway. In addition, the expression of miR-214 was decreased in OVX rats (P<0.01), and it was negatively correlated with the osteogenic differentiation of BMSCs (P<0.01). MiR-214 mimic inhibited Wnt signaling pathway in BMSCs (P<0.05 or P<0.01). Conversely, PT effectively counteracted the effect of miR-214 mimic, thereby activating the Wnt signaling pathway and stimulating osteogenic differentiation in BMSCs (P<0.05 or P<0.01). PT stimulates bone formation in OVX rats through β-catenin-mediated Wnt signaling pathway, which may be related to inhibiting miR-214 in BMSCs.

ETHNOPHARMACOLOGICAL RELEVANCE:Rehmanniae Radix Praeparata (RRP), a widely used traditional Chinese medicine and a processed form of Rehmannia glutinosa, is primarily utilized to supplement kidney function and promote bone health. Clinical evidence suggests that RRP exhibits significant efficacy in the treatment of osteoporosis (OP). However, the precise mechanisms underlying its therapeutic effects remain incompletely understood. AIM OF THE STUDY:OP is a systemic skeletal disorder characterized by reduced bone density and quality, leading to an increased risk of fractures. The aim of this study is to evaluate the effectiveness and underlying mechanisms of RRP in treating OP. MATERIALS AND METHODS:Ovariectomized (OVX) rats were administered RRP aqueous extract via gavage for three months. After the treatment period, femoral microstructure and osteogenic protein levels were assessed to evaluate the efficacy of RRP. Serum exosomes (Exos) derived from different groups of rats were isolated and characterized. The levels of miR-29a-3p in serum-derived Exos and femoral tissue were quantified. Subsequently, Exos were co-cultured with rat bone marrow mesenchymal stem cells (rBMSCs) to investigate their role in promoting osteogenic differentiation and explore the molecular mechanisms underlying this process, particularly through the miR-29a-3p/NFIA/Wnt signaling pathway axis. RESULTS:OVX rats exhibited significant bone microdamage. In contrast, the RRP-treated OVX rats showed marked improvements in femoral bone microstructure and increased osteogenic protein expression. MiR-29a-3p levels were elevated in serum-derived Exos from the RRP-treated rats. Furthermore, rBMSCs treated with these Exos displayed an increase in miR-29a-3p expression. Further investigations revealed that miR-29a-3p promoted osteogenesis by inhibiting NFIA expression in both bone tissue and rBMSCs. Overexpression of NFIA reversed the osteogenic effects of miR-29a-3p, confirming NFIA as its direct target and suggesting that miR-29a-3p enhances osteogenesis by inhibiting NFIA. Additionally, NFIA was found to promote the transcription of SFRP1, an inhibitor of the Wnt signaling pathway. Our findings suggest that the RRP aqueous extract increases miR-29a-3p levels in serum Exos, which in turn inhibits NFIA and activates the Wnt signaling pathway, thereby promoting osteogenesis. CONCLUSION:These findings suggest that the RRP aqueous extract improves bone health and mitigates bone microstructural damage caused by OP through the regulation of the miR-29a-3p/NFIA/Wnt signaling pathway axis.

Background: Osteoradionecrosis (ORN) is a serious complication of radiotherapy for head and neck cancer. There is currently a lack of data on the dynamic expression of genes related to bone remodeling during the development of mandibular ORN. This study aimed to establish an animal model of ORN in Sprague Dawley (SD) rats, detect the expression of genes related to bone metabolism, observe morphological changes, and clarify the mechanism of ORN. Methods: A total of 24 male SD rats in group 1 were randomly divided into four groups (n=6/group): group a, normal control; group b, simple tooth extraction; group c, simple radiation; and group d, radiation extraction group. The right mandible of rats in groups c and d was irradiated with a single dose of 35 Gy. The right mandibles were taken from each group for morphological observation 90 days after irradiation. SD rats in group 2 (n=144) were randomly divided into four groups (in similar fashion to group 1 but with groups a', b', c', and d'). Samples were collected at six time points after irradiation. Histopathological changes were observed, and Western blotting (WB) was used to analyze protein expression. Results: The formation of dead bone and pathological fracture was visible under micro-computed tomography (micro-CT), and tissue biopsy showed late fibrosis repair. In group d', osteogenesis and osteoclasis coexisted in the early irradiation stage. Vascular endothelial growth factor (VEGF) receptor expression was lower in groups c' and d' than in group a'. On day 45, runt-related transcription factor 2 (RUNX2) expression in group d' was lower than that in the other groups. The ratio of receptor activator of nuclear factor-kappa beta ligand to osteoprotegerin (RANKL:OPG) differed significantly among groups b', c', and d' on the 45th day (d' > c' > b'). Conclusions: Radiation and vascular function damage resulted in the lower expression of VEGF. The first 15 days after radiation was mainly characterized by new bone formation. After 15 days, bone resorption increased. Tooth extraction trauma can aggravate the bone metabolism imbalance and promote ORN occurrence. These findings shed light on the mechanism of ORN.

BACKGROUND:Lumbar disc herniation (LDH), as one of the most common causes of lower back pain, imposes a heavy economic burden on patients and society. Conservative management is the first-line choice for the majority of LDH patients. Traditional Chinese medicine (TCM) is an important part of conservative treatment and has attracted more and more international attention.STUDY DESIGN:Evidence-based guideline.METHODS:We formed a guideline panel of multidisciplinary experts. The clinical questions were identified on the basis of a systematic literature search and a consensus meeting. We searched the literature for direct evidence on the management of LDH and assessed its certainty-generated recommendations using the grading of recommendations, assessment, development, and evaluation (GRADE) approach.RESULTS:The guideline panel made 20 recommendations, which covered the use of Shentong Zhuyu decoction, Shenzhuo decoction, Simiao San decoction, Duhuo Jisheng decoction, Yaobitong capsule, Yaotongning capsule, Osteoking, manual therapy, needle knife, manual acupuncture, electroacupuncture, Chinese exercise techniques (Tai Chi, Baduanjin, or Yijinjing), and integrative medicine, such as combined non-steroidal anti-inflammatory drugs, neural nutrition, and traction. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement.CONCLUSION:This is the first LDH treatment guideline for TCM and integrative medicine with a systematic search, synthesis of evidence, and using the GRADE method to rate the quality of evidence. We hope these recommendations can help support healthcare workers caring for LDH patients.

Bone homeostasis encompasses two interrelated aspects: bone remodeling and cartilage metabolism. Disruption of bone homeostasis can lead to the development of metabolic bone diseases such as osteoporosis and osteoarthritis. The maintenance of bone homeostasis is a complex process that does not solely rely on the functions of the bone tissue itself. In fact, bone tissue is not an isolated entity; it is closely connected to other tissues in the body via exosomes. Within this interconnectivity, exosomes derived from both bone and non-bone cells interfere with each other, forming a complex regulatory network. Therefore, with cell origin as the guiding principle, we have delineated the bone regulatory network of exosomes, elaborated on the specific roles and regulatory mechanisms of exosomes derived from common cell types (cells within the skeletal microenvironment, stem cells from extra-osseous tissues, vascular-derived cells, muscle-derived cells, and neurogenic cells) in bone formation, bone resorption, and cartilage metabolism. We have also discussed the challenges faced in the field of exosome research related to bone homeostasis, unveiled the critical role of exosomes in maintaining bone homeostasis, and proposed that exosomes could serve as highly valuable therapeutic targets for metabolic bone diseases.

The role of estrogen receptor β (ERβ) in bone health is closely associated with its function in vivo, and ERβ−/− mice have been widely utilized to explore the related influences. In this study, ERβ−/− female mice were established to investigate the differential expression of circular RNAs (circRNAs) by RNA-Sequencing (RNA-Seq). Among these circRNAs, mmu_circ_0011379 (named Circ-Spen) exhibited high expression in ERβ−/− female mice. However, the precise mechanism by which Circ-Spen regulates bone health remained unclear. This study identified Circ-Spen as a positive regulator of mouse bone marrow mesenchymal stem cell (mBMSC) viability. The expression of Circ-Spen was markedly increased in ERβ−/− mice femurs tested by RT-qPCR. Moreover, Circ-Spen exhibited an enhanced expression during the bone formation process of mBMSCs. Qualitative experiments also demonstrated that Circ-Spen possessed a circular structure and was localized within the nucleus of mBMSCs. Functionally, it inhibited apoptosis via caspase-3, BCL-2, and BAX, while also promoting autophagy through BECN1 and P62 in mBMSCs tested by MTT assays, transmission electron microscopy (TEM), and Western blotting. These findings reveal the potential of targeting Circ-Spen as a promising therapeutic strategy for rejuvenating senescent mBMSCs and enhancing the efficiency of mBMSC transplantation, which lays the foundation for advancements in the field of bone therapy.

Despite the diverse roles of tripartite motif (Trim)-containing proteins in the regulation of autophagy, the innate immune response, and cell differentiation, their roles in skeletal diseases are largely unknown. We recently demonstrated that Trim21 plays a crucial role in regulating osteoblast (OB) differentiation in osteosarcoma. However, how Trim21 contributes to skeletal degenerative disorders, including osteoporosis, remains unknown. First, human and mouse bone specimens were evaluated, and the results showed that Trim21 expression was significantly elevated in bone tissues obtained from osteoporosis patients. Next, we found that global knockout of the Trim21 gene (KO, Trim21 −/− ) resulted in higher bone mass compared to that of the control littermates. We further demonstrated that loss of Trim21 promoted bone formation by enhancing the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and elevating the activity of OBs; moreover, Trim21 depletion suppressed osteoclast (OC) formation of RAW264.7 cells. In addition, the differentiation of OCs from bone marrow-derived macrophages (BMMs) isolated from Trim21 −/− and Ctsk-cre; Trim21 f/f mice was largely compromised compared to that of the littermate control mice. Mechanistically, YAP1/β-catenin signaling was identified and demonstrated to be required for the Trim21-mediated osteogenic differentiation of BMSCs. More importantly, the loss of Trim21 prevented ovariectomy (OVX)- and lipopolysaccharide (LPS)-induced bone loss in vivo by orchestrating the coupling of OBs and OCs through YAP1 signaling. Our current study demonstrated that Trim21 is crucial for regulating OB-mediated bone formation and OC-mediated bone resorption, thereby providing a basis for exploring Trim21 as a novel dual-targeting approach for treating osteoporosis and pathological bone loss.

Objective: Percutaneous coronary intervention is one of the most common procedures used for the invasive treatment of patients with coronary heart disease; the incidence of in-stent restenosis (ISR) after percutaneous coronary intervention is 5% to 15%. In this study, a competitive endogenous RNA (ceRNA) network was constructed to investigate potential mechanisms involved in ISR. Methods: The expression data for differentially expressed microRNAs (DEmiRNAs) and messenger RNAs (mRNAs) between patients with and without ISR were obtained using limma package. Long noncoding RNAs (lncRNAs) were predicted based on the DEmiRNAs using the miRDB, miRTarBase, and TargetScan databases. An ISR-specific ceRNA network was subsequently constructed and investigated. To verify the key miRNAs of ceRNA, patients with and without ISR were enrolled from Guangdong Provincial Hospital of Chinese Medicine between January 2017 and December 2018 ( n = 8, respectively); plasma was collected from all enrolled patients. Results: Based on the raw data obtained from the Gene Expression Omnibus database, 472 DEmiRNAs and 304 differentially expressed messenger RNAs between patients with and without ISR were identified. A ceRNA network was constructed by combining 270 lncRNAs, 3 miRNAs (miR-125, miR-140, and miR-206), and 4 mRNAs (STRADB, TKT, PCTP, and BTG2). The hub genes of the ceRNA network of ISR included the following: miR-125, miR-206, miR-140, PCDHB9, CASC2, BAK1P1, CSPG4P3Y, CSPG4P4Y, STRCP1, and GRIP2. Verification of miRNAs of ceRNA also showed that the expression of miR-206 was upregulated in patients with ISR vs . those without ISR ( P < 0.05). In contrast, the expression of miR-140 and miR-125 was downregulated in patients with ISR vs . those without ISR ( P < 0.05). Conclusions: This study constructed noncoding RNA-related ceRNA networks for ISR. The results indicated that miR-206, miR-125, and miR-140 may be biomarkers of ISR.

[目的/意义]在学术思想和观点抽取及主题挖掘的基础上对图书情报领域学术思想和观点发展轨迹进行整理、归纳和总结,不仅有助于从历时的角度梳理图书情报学的发展历程,而且有益于从微观视角探寻图书情报学所取得的成就.[研究设计/方法]基于1992-2022年间图书情报领域的核心期刊论文,对图书情报学的学术思想和学术观点进行相应的界定和梳理;制定针对学术思想和学术观点的标注规范并完成人工标注,进而基于深度学习模型构建学术思想和学术观点自动抽取模型;而后结合主题模型,以时间为主序列,系统地探究图情学术思想和学术观点的发展轨迹.[结论/发现]图情学科各时段代表性学术思想主题有阮氏分类思想、目录学思想、引文分析、知识管理等,代表性学术观点主题有读者服务、认知情报学、学科馆员、舆情演化等.各时段的学术思想和学术观点与该时段图书情报学科发展主题相呼应,一方面学术思想及其观点在学科发展中发挥了基础性作用,具有稳定性;另一方面新问题的出现又驱动其他学科思想和观点的引入以及新思想和新观点的产生,具有动态变化性.[创新/价值]基于数据驱动的方式梳理图情领域学术思想和学术观点的发展,不仅弥补了传统方法的不足,也为学者了解图书情报学的历史演变和未来预测提供了新的思路.

目的:探讨熟地黄(Rehmanniae Radix Praeparata,RR)水提液对双侧卵巢切除(ovariectomy,OVX)大鼠脂代谢紊乱的影响及作用机制.方法:将40只3月龄SD雌性大鼠随机分为5组,分别为假手术组、OVX组、RR水提液低剂量组、RR水提液中剂量组和RR水提液高剂量组,对大鼠分别行假手术或OVX,药物灌胃12周后取材,测定大鼠的体重、腹围、血清雌二醇(estradiol,E2)、子宫重量、胰岛素(insulin,INS)和血脂四项;行肝脏HE染色和油红O染色观察脂质积累;行腹部脂肪HE染色观察脂肪体积;Western blot和RT-qPCR检测腹部脂肪过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptorγ,PPARγ)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)和白细胞介素1β(interleukin,IL-1β)的表达;RT-qPCR检测肥胖相关因子糖蛋白非转移性黑色素瘤蛋白B(glycoprotein non-metastatic melanoma protein B,GPNMB)、血清外泌体miR-29a-3p、腹部脂肪miR-29a-3p及其靶基因核因子I A(nuclear factor I A,NFIA)的表达;Western blot检测腹部脂肪Wnt信号通路相关蛋白的表达.结果:RR水提液显著降低OVX大鼠的腹围、INS、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)、肝脏脂质积累、腹部脂肪细胞扩张、PPARγ、TNF-α、IL-1β、GPNMB和NFIA的表达,显著升高OVX大鼠的血清E2、血清外泌体miR-29a-3p和腹部脂肪miR-29a-3p水平,激活腹部脂肪Wnt信号通路.结论:RR水提液可降低OVX大鼠的血清E2、INS、LDL-C和肝脏脂质积累,抑制腹部脂肪细胞扩张和炎症反应,其作用机制可能是与血清外泌体中miR-29a-3p和腹部脂肪中miR-29a-3p的含量增加后致NFIA表达量下降,从而激活腹部脂肪组织中Wnt信号通路有关.

[目的/意义]在加快构建中国特色哲学社会科学话语体系的背景下,探究我国在国际图书情报领域学科话语权,有助于传播学科话语,提升我国在国际图情领域的学科地位.[方法/过程]文章首先借助话语研究方法论剖析国际图情领域学科话语权形成过程;在此基础上,融入场域理论构建国际图情领域学科话语权形成机制模型,探究我国在国际图情领域生产、表达、传播学科话语权的特点与演化轨迹;最后从学科多样性与学科差异性两个维度,测度各国的学术研究视野广度与研究领域跨度,进而剖析我国在国际图情领域学科话语权地位.[结果/结论]研究发现:国际图情领域学科话语权的形成是6个学科话语形成要素有机配合、相互作用的循环运作过程;其演化过程,无论是在其生产、表达,还是传播环节都始终坚持质量为先;国际图情领域我国学科话语权居于引领地位,核心优势取决于与计算机科学相关的跨学科研究,竞争优势在于地理学相关学科的跨领域研究.

ScopeGlycine is commonly used as an additive in bone health supplements, the activity and differentiation of bone mesenchymal stem cells (BMSCs) are essential to bone metabolism, but the effect of Glycine on bone metabolism and specific mechanism are not fully clarified.Methods and resultsThe ovariectomized rats to evaluate the effects of Glycine on bone quality and quantity is constructed; then used an ER signaling inhibitor (ICI182780) and an ERα deficient BMSCs to explore how Glycine mediated ERα regulating the osteogenic and adipogenic differentiation of BMSCs; furthermore, an autodock analysis is used to assess the affinity of Glycine and ERα. The results show that Glycine significantly moderated bone mass and bone microstructure in ovariectomized rats; Glycine stimulates the osteogenic differentiation and attenuates the adipogenic differentiation in OVX rats and BMSCs, and these effects could be abolished by ICI 182780; further docking experiment showes that Glycine and ERα have a stronger affinity, and finally proves that the impact of Glycine could be blocked by ERα.ConclusionGlycine stimulates osteogenesis and attenuates adipogenesis in ovariectomized rats, which process may involve in ERα mediated ER signaling pathway.

To investigate the association between blood routine (BRT) parameters and bone loss as well as the possible mechanism of this association with bone loss in the middle- aged and elderly patients. A total of nine hundred and ninety-eight subjects (the total) aged≥40 years in General Hospital of Southern Theater Command of People's Liberation Army from March 2015 to January 2018 were enrolled in a cross-sectional studyPatients were divided into two groups as "at least osteopenia group" (including osteopenia, osteoporosis, and severe osteoporosis) and "normal group" according to the diagnosis standard of OP. The above indicators were analyzed and compared between the two groups. Binary multivariate logistic regression analysis was carried out to explore the association between BRT parameters and risk of bone loss in the subjects Mediation Effect was conducted to test endocrine variables as mediators in the correlation of BRT parameters with the bone loss for the possible mechanisms. There were 669 cases in the at least osteopenia group and 329 in the normal group. RBC, Hb, HCT and MCHC were all positively correlated with BMD of lumbar spine(L1-4), left femoral neck and left femur, along with lymph positively correlated with BMD of left femoral neck and left femur, respectively. Eosinophils(Eo) was positively correlated with BMD of L1-L4 and RDW-SD together with RDW-CV were both negatively correlated with BMD of left femoral neck and left femur. By binary multivariate logistic regression, only Hb was associated with bone loss and the OR value was 0.478 as protective factor for BMD. Estradiol (E2) and testosterone (T) had partial mediating effect on the association of BRT parameters with the risk of bone loss. The mediating effect of E2 on the relationship between WBC and bone loss accounted for 46.35% of the total effect, and that of T on the relationship between RBC, Hb, HCT, MCHC and bone loss accounted for 27%, 18.3%, 31.1% and 26.8%, respectively. Bone loss in the middle-aged and elderly population is accompanied with the change of BRT parameters and the erythrocyte indices tend to be more obvious especially the Hb, which indicates anemia had a potential connection with bone loss. Sex hormone, especially T, is an important mediating variable in the association between blood routine parameters and bone loss.