Osteoclasts and osteoblasts play critical roles in bone remodeling, and their dysregulation leads to pathological bone loss. However, the precise mechanisms underlying the regulation of differentiation remain unclear. This study investigated the role of the transcriptional regulator Zinc Finger Matrin-Type 1 (Zmat1) in both osteoclastogenesis and osteoblastogenesis. Zmat1 deficiency resulted in decreased osteoclast activity, and bone resorption. Mechanistically, ZMAT1 was significantly upregulated during osteoclast differentiation and acted as a transcriptional repressor of the E3 ubiquitin ligase TRIM46, which regulates YAP1 degradation via K48-linked ubiquitination. Furthermore, Zmat1 deficiency enhanced osteoblast activity and bone formation. These findings highlight a novel ZMAT1/TRIM46/YAP1 axis, providing new insights into the transcriptional regulation of both osteoclast and osteoblast differentiation, and present potential therapeutic targets for osteoporosis.

The use of piezoelectric materials to convert micromechanical energy at the fracture site into electrical signals, thereby modulating stress-concentrated inflammation, has emerged as a promising treatment strategy for diabetic fractures. However, traditional bone-guiding membranes often face challenges in diabetic fracture repair due to their passive and imprecise drug release profiles. Herein, a piezoelectric polyvinylidene fluoride (PVDF) fibrous membrane is fabricated through electrospinning and oxidative polymerization to load metformin (Met) into a polypyrrole (PPy) coating (Met-PF@PPy), creating a "mechanical-electrical-pharmaceutical coupling" system. In a micromotion mechanical environment, Met-PF@PPy converts mechanical energy into electrical signals, activating the electrochemical reduction of PPy and triggering stress-responsive Met release. The generated electrical signals suppress inflammation through M1-to-M2 macrophage polarization and simultaneously enhance osteogenesis. Simultaneously, Met inhibits the NF-κB pathway to reduce pro-inflammatory cytokines while activating the AMPK pathway to promote osteogenesis and angiogenesis. In a diabetic mouse femoral fracture model, Met-PF@PPy significantly reduces inflammatory markers, enhances vascularization, and increases bone mineral density and bone volume fraction by over 30%. This "force-electric-drug coupling" strategy provides an innovative approach for active regulation in diabetic fracture repair and offers a versatile platform for advancing piezoelectric materials in regenerative medicine.

Negative‐pressure wound therapy plays a pivotal role in treating open bone fractures. However, the loss of bioelectricity during the healing process significantly delays tissue repair. The generation and maintenance of bioelectric fields require a complex interplay of multiple factors. Previous attempts to regenerate the lost bioelectric field using exogenous conductive materials or supplementing endogenous functional electrolytes have limited success. During this study, a novel electroactive dressing is formulated tailored for negative‐pressure therapy by combining piezoelectric poly L‐lactic acid doped with bioactive glass and amino‐terminated dendritic macromolecules. When subjected to negative pressure, the mechanical deformation of the dressing generates exogenous piezoelectric signals that effectively couple with the endogenous ionic electric fields. Furthermore, the amine‐terminated poly(amidoamine) dendritic macromolecules capture cations via coordination and ion‐exchange mechanisms, thus retaining electrolytes at the wound site. The findings indicate that the bioelectricity generated by the electroactive dressing under negative pressure facilitates the influx of calcium ions into cells. Calcium ions bind calmodulin, activating Ca 2 ⁺/calmodulin‐dependent kinase II, which further activates phosphatidylinositol3‐kinase (PI3K), initiating the PI3K/Akt pathway and enhancing osteoblast activity. The efficacy of the developed electroactive dressing is verified using a critical‐sized cranial bone‐defect model in rats, demonstrating its significant osteogenic differentiation potential. The exogenous and endogenous fields provided by the electroactive dressing maintain the electrophysiological state necessary for bone regeneration, providing a novel therapeutic approach for clinical open fractures.

OBJECTIVE:To compare the clinical efficacy of the minimally invasive locking plate technique (Philos plate) and interlocking intramedullary nailing technique (TRIGEN intramedullary nail) in the treatment of Neer two-part and three-part proximal humeral fractures. METHODS AND MATERIALS:The clinical data of 60 patients with Neer two-part and three-part proximal humerus fractures admitted to the hospital from April 2017 to April 2021 were retrospectively analyzed. Thirty-two patients were treated with the minimally invasive locking plate technique (minimally invasive plate group), and 28 patients were treated with the interlocking intramedullary nailing technique (intramedullary nail group). The operation time, intraoperative blood loss, incision length, fracture healing time, and postoperative complications were compared between the two groups. The ASES score and Constant-Murley score were used to evaluate the shoulder joint function of the two groups one year after surgery. RESULTS:All 60 patients were followed up for 12 to 24 months, with an average of 16 months. There was no significant difference in operation time, intraoperative blood loss, incision length, or fracture healing time between the two groups (P > 0.05). The incidence of postoperative complications in the intramedullary nail group was significantly lower than that in the minimally invasive steel plate group, and the difference between the groups was statistically significant (P < 0.05). There was no significant difference in the ASES score or Constant-Murley score between the two groups one year after surgery (P > 0.05). CONCLUSION:The use of the minimally invasive locking plate technique and interlocking intramedullary nailing technique in the treatment of Neer two-part and three-part proximal humerus fractures has the advantages of a small incision, less blood loss, and a high fracture healing rate, and both can achieve satisfactory clinical effects. The internal nail technique is more convenient than the minimally invasive locking plate technique in controlling postoperative complications.

Background: This study aims to compare therapeutic effects of two methods in complicated subtrochanteric femur fractures surgery: intramedullary nail fixation assisted with lateral monocortical locking plate versus intramedullary nail fixation assisted with supplementary cables.Methods: From June 2015 to June 2020, seventy-seven patients with complex subtrochanteric fractures (i.e., Seinsheimer's classification type IV or V) were included in this study. Thirty-six patients (plate group) were operated using the intramedullary nail fixation assisted by lateral monocortical locking plate, and forty-one patients (cable group) were using the intramedullary nail fixation assisted by cables. The clinical information and demographic results were collected and compared.Results: Operation time of plate group was shorter than cable group and the Incisions length of plate group was longer. The fluoroscopy times were 22.8 +/- 8.2 in plate group and 33.0 +/- 9.0 in cable group (p < 0.01). Compared with the cable group, patients in plate group used less cerclage cables (p < 0.01). Patients in the plate group has less medial cortex displacement compared with the cable group. (p 1/4 0.038). As for the angular difference of neck shaft angle between operated hip and uninjured hip, plate group has less difference compared with the cable group. Time to union was 14.2 +/- 3.1 weeks in plate group which is shorter than the cable group (17.9 +/- 4.8 weeks). In terms of follow up period, number of malunion, Harris hip score, walking ability and traumatic hip rating scale, no significant differences were detected.Conclusions: Our results suggest that using lateral monocortical plate as an auxiliary way may have a longer surgical incision and more intraoperative blood loss, however, the operation time is shorter, the fluoroscopy times is less, and the time to union is shorter. Intramedullary nail fixation assisted by lateral monocortical locking plate may be a new option for patients with complex subtrochanteric femur fractures.

Bone related infections elicit excessive inflammatory responses, progressive osteolysis, and persistent bacterial load, which impede bone regeneration. Conventional antibiotics can mitigate bacterial load; however, they fail to inhibit bone resorption and the inflammatory response. To enhance bone regeneration during bacterial infection, an optimal therapeutic strategy should not only eradicate bacteria but also inhibit inflammation and osteolysis. In this study, we fabricated a multi-biofunctional coating, designated MSNs-BMP4-EN, by covalently immobilizing mesoporous silica nanoparticles (MSNs) with human bone morphogenetic protein 4 (BMP4) and loading with enoxacin (EN) for antibacterial effect with inhibiting inflammation and osteolysis. Antimicrobial assessments revealed that MSNs-BMP4-EN markedly obstructed bacterial adhesion and colonization. Subsequent in vitro assessments demonstrated that it facilitated osteogenic differentiation of bone mesenchymal stem cell and impeded early osteoclastogenesis. Moreover, MSNs-BMP4-EN effectively restrained the secretion of pro-inflammatory mediators, thereby counteracting the infection-induced inflammatory milieu and promoting bone regeneration. Collectively, these findings indicate that MSNs-BMP4-EN exhibits excellent antibacterial, anti-inflammatory, and bone resorption inhibitory attributes during initial stages of bone-related infection, thereby further improving bone regeneration. As a result, this bioactive nanocomposite has excellent prospects for treating bone infections.

OBJECTIVE:This study was to compare the efficacy of femoral nerve block (FNB) and acupuncture for acute preoperative pain in patients with femoral neck fracture (FNF).METHODS:From June 2017 to June 2019, 130 patients with FNF were included in this study. Sixty-six patients received FNB treatment (FNB group) and sixty-four patients received acupuncture treatment (Acupuncture group). The clinical information, visual analog scale (VAS) scores, nursing quality scores, sleep quality scores, delirium numbers, and perioperative complications were collected and compared between the 2 groups.RESULTS:The resting VAS score and the exercise VAS score decreased after FNB or acupuncture in both groups. Thirty minutes after analgesia, the resting VAS scores in the FNB group and the acupuncture group were 27.3±8.0 and 27.9±7.8, respectively (P=0.67); while exercise VAS scores were 60.2±10.4 and 59.5±9.8, respectively (P=0.73). In addition, there was no statistical difference in the VAS score between the two groups on day 1 and day 2 after admission. There was no statistical difference in nursing quality, sleep rhythm disorder, sleep quality, or times of mental disorder between the two groups.CONCLUSION:FNB analgesia and acupuncture analgesia are safe and effective for the control of acute preoperative pain in senile patients with femoral neck fracture. Both methods have good analgesic effects, which can improve nursing and sleep quality, and reduce the incidence of delirium. As a traditional Chinese medicine method, acupuncture analgesia can effectively manage the acute preoperative pain in senile femoral neck fracture patients.

The bone marrow microenvironment is composed primarily of immune and stromal cells that play important roles in fracture healing. Although immune cells have been identified in mouse bone marrow, variations in their numbers and type during the fracture healing process remain poorly defined. In this study, single-cell RNA sequencing was used to identify immune cells in fracture tissues, including neutrophils, monocytes, T cells, B cells, and plasma cells. The number of B cells decreased significantly in the early stage of fracture healing. Furthermore, B cells in mice fracture models decreased significantly during the epiphyseal phase and then gradually returned to normal during the epiphyseal transformation phase of fracture healing. The B-cell pattern was opposite to that of bone formation and resorption activities. Notably, B-cell–derived exosomes inhibited bone homeostasis in fracture healing. In humans, a decrease in the number of B cells during the epiphyseal phase stimulated fracture healing. Then, as the numbers of osteoblasts increased during the callus reconstruction stage, the number of B cells gradually recovered, which reduced additional bone regeneration. Thus, B cells are key regulators of fracture healing and inhibit excessive bone regeneration by producing multiple osteoblast inhibitors.

BACKGROUND:The unstable intertrochanteric femur fracture remains a challenge for surgeons. However, few studies have compared the clinical effectiveness of intramedullary nail in combination with a reconstruction plate and intramedullary nail alone in the treatment of patients with unstable intertrochanteric femoral fractures with lateral wall damage.METHODS:This study retrospectively analyzed 16 patients with 31 A3 intertrochanteric fractures treated with the intramedullary nail in combination with reconstruction plate (the study group) and 19 patients with 31 A3 intertrochanteric fractures treated with intramedullary nail alone (the control group) between January 2012 and January 2018. The operation time, intra-operative blood loss, time of fracture healing, and complication rates of post-operative fixation failure were assessed between the two groups. At the follow-up of post-operative six and 12 months, Harris hip score (HHS) and the Parker-Palmer mobility score (PPMS) were used to evaluate the functional states and mobility levels.RESULTS:The distribution of all basic characteristics was similar between the two groups (P ˃ 0.05). The study group had longer operation time and more intra-operative blood loss in comparison with the control group (P < 0.001), while the study group had shorter fracture healing time (P = 0.03) and lower fixation failure rate as compared with the control group. Regarding the functional outcome, the study group had higher HHSs and PPMS than the control group (P = 0.003).CONCLUSIONS:Although intramedullary nails in combination with reconstruction plates had longer operation time and more intra-operative blood loss, it might be superior to intramedullary nail alone in terms of fracture healing time, fixation failure complication rate, and post-operative functional recovery.

The regulation of bone formation and detailed mechanisms are still largely elusive, and the roles of microRNAs in this process have attracted much attention. Recently, a specific subtype of CD31hiendomucinhi (CD31hiEMCNhi) endothelium has been identified to promote bone formation, together with osteoblast development. However, the role of microRNA143 in the generation of CD31hi EMCNhi endothelium and bone formation remains unknown. In this study, we found that miR-143 was expressed both in osteoblast cells and CD31hiEMCNhi endothelial cells. Serum miR-143 level was negatively correlated with age in humans. Overexpression of miR-143 promoted osteoblast formation and angiogenic effects. Furthermore, CD31hiEmcnhi vessels and osteoblast formation were significantly inhibited in miR-143 knockout mice. Mechanistically, inhibitor HDAC7 was directly targeted by miR-143 and knockdown of HDAC7 was found to rescue the function of miR-143 deficiency. Thus, miR-143 promotes angiogenesis coupling with osteoblast differentiation by targeting HDAC7, which may serve as a potential target in angiogenic and osteogenic diseases.

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. However, the underlying mechanism of osteosarcoma carcinogenesis and progression remains unknown. In the present study, we evaluated the expression profile of miRNAs in osteosarcoma tissues and the adjacent normal tissues. We found that the expression of miR-422a was down-regulated in osteosarcoma tissues and cell lines. In addition, we observed significantly elevated levels of repressive H3K9me3 and H3K27me3 and decreased active H3K4me3 on the promote region of miR-422a in osteosarcoma cells and clinical samples. Furthermore, up-regulation of miR-422a exhibited both in vitro and in vivo anti-tumor effects by inhibiting osteosarcoma cell growth and inducing apoptosis and cell cycle arrest. We also found that miR-422a targeted BCL2L2 and KRAS and negatively regulated their protein expression. Furthermore, restoration of miR-422a and knockdown of BCL2L2 and KRAS promoted apoptosis and induce cell cycle arrest in osteosarcoma cells. Taken together, the present study demonstrates that miR-422a may serve as a tumor suppressor in osteosarcoma via inhibiting BCL2L2 and KRAS translation both in vitro and in vivo. Therefore, miR-422a could be developed as a novel therapeutic target in osteosarcoma.

Titanium (Ti) and its alloys are widely applied as orthopedic implants for hip and knee prostheses, fixation, and dental implants. However, Ti and its alloys are bioinert and susceptible to bacteria and biofilm formation. Thus, surface biofunctionalisation of Ti is essential for improving the biofunction of Ti. The current in vitro study indicated that calcium phosphate bone cement with vancomycin doped on micro-patterned Ti with a grid-like structure surface could preserve the property of inhibition of bacterial adhesion and biofilm formation while not affecting the osteogenic differentiation. The present study investigated whether the biological performance of the bactericidal effect is preserved in vivo. The rabbit osteomyelitis model with tibial medullary cavity placement of Ti rods was employed to analyze the antibacterial effect of vancomycin-loaded Ti coatings with interconnected micro-patterned structure (TV). Thirty female rabbits (N = 10) were used to establish the implant-associated infection. Prior to implanting the T0 and TV rods into the medullary cavity of the left tibia of the rabbits, 106 CFU mL-1 methicillin-resistant Staphylococcus aureus (MRSA) was injected into the medullary cavity of the left tibia of the rabbits. The sterile Ti rod (NT) was used as the blank control. After 3 weeks, bone pathology was evaluated using X-ray and micro-CT. The in vivo study proposed that TV has the potential for prophylaxis against MRSA infection. Thus, the interconnected micro-patterned structured Ti rods loaded with vancomycin could be applied for preventing Ti implant-associated infections.

Traditional incision repair and minimally invasive repair for acute Achilles tendon repair have limitations. This study aimed to present our series of 23 patients with acute Achilles tendon rupture that was repaired using two small incisions to assist the anchor repair of the tear and a new “circuit” suture technique.

Deregulated expression of circular RNA (circRNA) has been determined to be important in carcinogenesis and progression; however, in the most common type of primary malignant bone tumor osteosarcoma, the roles of circRNA in cancer development still remain to be elucidated. Here, we found that circRNA UBAP2 (circUBAP2) expression is significantly increased in human osteosarcoma tissues as compared to those in matched controls. Increased circUBAP2 expression was significantly correlated with human osteosarcoma progression and prognosis. Furthermore, increased circUBAP2 could promote osteosarcoma growth and inhibit apoptosis both in vitro and in vivo. Mechanistically, circUBAP2 was found to inhibit the expression of microRNA-143 (miR-143), thus enhancing the expression and function of anti-apoptotic Bcl-2, which is a direct target of miR-143. Together, our results suggest the roles of circUBAP2 in osteosarcoma development and implicate its potential in prognosis prediction and cancer therapy.

The present study aimed to investigate the effects of micro-patterned titanium coatings doped with vancomycin on antibacterial activity and osteogenic differentiation and to improve the bioactivity of the inert titanium..

We aim to investigate the effect of miR-106a-5p on the proliferation, migration, and invasion of osteosarcoma (OS) cells by targeting high-mobility group AT-hook 2 (HMGA2). Real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) was used for detecting the expressions of miR-106-5p and HMGA2 in 137 OS and adjacent normal bone tissues. Immunohistochemistry was applied for the HMGA2 protein expression detection. Luciferase reporter gene assay was conducted for verifying whether miR-106-5p targeted HMGA2. MG63 and U2SO cells were respectively divided into five groups: Blank, miR-106a-5p, scramble, HMGA2-siRNA, and miR-106a-5p+HMGA2 groups. RT-qPCR and western blot were applied for detecting the expressions of miR-106a-5p and HMGA2 in five groups. Proliferation rate, cell cycle, invasion, and migration ability of OS cells were detected using methyl thiazolyl-tetrazolium, 5-ethynyl-2'-deoxyuridine (Edu) assay, flow cytometry, and Transwell.  Compared with adjacent normal tissues, OS tissues presented with decreased miR-106a-5p expressions, elevated HMGA2 mRNA, and positive expressions (all p < 0.05). The sensitivity and specificity of miR-106a-5p were 97.8%, 93.43%, and HMGA2 mRNA were 97.8%, 99.27%, separately. miR-106a-5p and HMGA2 expressions were associated with tumor size, Enneking stage, distant metastasis, and lung metastasis. Expressions of HMGA2 in OS cells in miR-106a-5p and HMGA2 siRNA groups were both significantly decreased with the same downregulation level, and the proliferation rates in both groups were obviously slowed down after 48 h (both p < 0.001). Edu positive cells, S phase cells (majority of cells blocked at G0/G1 phase), migratory and invasive cells were obviously decreased (all p < 0.05). Downregulation of miR-106a-5p was found in OS tissues, and upregulation of miR-106a-5p can inhibit the proliferation, migration, and invasion by targeting HMGA2 in OS cells.

Osteosarcoma is the most common type of primary malignant bone tumor, and deregulated microRNAs (miRNAs or miRs) in osteosarcoma have attracted great attention. In the present study, through miRNA microarray analysis, it was identified that miR-148a expression was significantly increased in osteosarcoma tissues. Increased miR-148a expression was significantly correlated with tumor progression and prognosis. Furthermore, increased miR-148a expression could promote osteosarcoma growth in vitro and in vivo, and the tumor-promoting effect was due to enhanced activation of the phosphoinositide 3-kinase signaling pathway caused by miR-148a-mediated inhibition of phosphatase and tensin homolog expression. Together, the present results suggest a role for miR-148a in osteosarcoma development and its potential use in prognosis prediction and cancer therapy.

Diverse functions of microRNAs have been investigated in tumorigenesis in osteosarcoma (OS), involving the regulation of proliferation, invasion, migration, apoptosis and drug resistance. MiR-367 was found to be an oncogene and increased in OS. However, the function of miR-367 in drug resistance in OS cells is still unknown. In this study, we found that miR-367 was up-regulated in OS tissues and OS cell cultures. Meanwhile, treatment with adriamycin (ADR) induced apoptosis of OS cells with upregulation of miR-367. Notably, KLF4 was demonstrated to be a direct target of miR-367 by gene reporter assay, and miR-367 significantly blocked both mRNA and protein level of KLF4. In addition, overexpression of miR-367 markedly suppressed the increase of KLF4 induced by ADR in OS cells, as well as Bax and cleaved caspase-3, which were significantly reversed by anti-miR-367 transfection. Taken together, our data demonstrates that miR-367 and KLF4 play important roles in OS treatment and ADR resistance, suggesting that miR-367 is a potential biomarker of chemotherapy resistance in OS and also probably a novel therapeutic target against OS.

Although many meta-analyses comparing surgical intervention with conservative treatment have been conducted for acute Achilles tendon rupture, discordant conclusions are shown. This study systematically reviewed the overlapping meta-analyses relating to surgical versus conservative intervention of acute Achilles tendon rupture to assist decision makers select among conflicting meta-analyses, and to offer intervention recommendations based on the currently best evidence. Multiple databases were comprehensively searched for meta-analyses comparing surgical with conservative treatment of acute Achilles tendon rupture. Meta-analyses only comprising randomized controlled trials (RCTs) were included. Two authors independently evaluated the meta-analysis quality and extracted data. The Jadad decision algorithm was applied to ascertain which meta-analysis offered the best evidence. A total of 9 meta-analyses were included. Only RCTs were determined as Level-II evidence. The scores of Assessment of Multiple Systematic Reviews (AMSTAR) ranged from 5 to 10 (median 7). A high-quality meta-analysis with more RCTs was selected according to the Jadad decision algorithm. This study found that when functional rehabilitation was used, conservative intervention was equal to surgical treatment regarding the incidence of rerupture, range of motion, calf circumference, and functional outcomes, while reducing the incidence of other complications. Where functional rehabilitation was not performed, conservative intervention could significantly increase rerupture rate. Conservative intervention may be preferred for acute Achilles tendon rupture at centers offering functional rehabilitation, because it shows a similar rerupture rate with a lower risk of other complications when compared with surgical treatment. However, surgical treatment should be considered at centers without functional rehabilitation as this can reduce the incidence of rerupture.