The repair of bone defects represents a coordinated process entailing interactions, including such as early immune-inflammation regulation, angiogenesis, osteogenic differentiation, and bone formation, among angiogenesis is crucial. Consequently, augmenting the angiogenic capacity of engineering materials has emerged as a pivotal strategy for effective bone regeneration. In this study, a nano pearl powder (NPP)/chitosan-hyaluronic acid (C-HA) composite bioactive scaffold was cultured with human umbilical vein endothelial cells (HUVECs) to evaluate its angiogenic potential in vitro. The NPP/C-HA scaffolds promoted HUVEC proliferation, with a cell proliferation rate of 1.49 % f 4.5 % and a cell count of 22 f 1.73 per field of view. Tubule formation was observed, with 101 f 33 junction points and 78 f 14 branch points. The relative protein expression levels of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR2), and basic fibroblast growth factor (bFGF) were increased. In vivo, the addition of NPP to the scaffolds enhanced the expression of vascular-related proteins, including platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) and VEGF. Simultaneously, microvessel density (MVD) increased to 19.51 f 4.60. These findings suggest that NPP/C-HA may be a promising biomaterial for bone repair and regeneration.
Bone defects, caused by trauma, osteomyelitis, or osteoporosis, represent a significant global health challenge in orthopedics. However, current bone repair strategies often neglect the critical role of the immune microenvironment, which can impede effective bone regeneration. To address this gap, we developed a 3D-printed triple crosslinked hydrogel scaffold incorporating slow-release glycopyrrolate (GA) and epigallocatechin gallate (EGCG), that it could promote bone regeneration by modulating the immune response. We evaluated their immunomodulatory and bone-regenerative effects through in vitro cellular experiments and rat cranial defect models. Results demonstrated that these scaffolds effectively modulated the immune microenvironment, reducing inflammation while promoting osteoblast differentiation and proliferation, thereby significantly enhancing new bone formation and density. In conclusion, our novel 3D-printed hydrogel scaffold offers a promising approach to bone defect repair through its unique combination of mechanical strength, immunomodulation, and osteogenesis. This study provides valuable insights into leveraging immunomodulatory agents for enhanced bone regeneration, highlighting potential clinical applications.
OBJECTIVE:Betel-chewing-related oral squamous cell carcinoma (BCR-OSCC) has become a global health issue with increasing incidence year by year around the world. Active prevention of the occurrence of BCR-OSCC, monitoring the population exposed to Betel Nuts, and early diagnosis and treatment are very important to maintain and improve the quality of life of patients. However, there is currently no consensus or guideline that provides targeted guidance on the management of BCR-OSCC. SUBJECTS AND METHODS:A consensus panel consisting of 15 leading Chinese experts from multidisciplinary fields was convened, and a roundtable meeting was held to discuss the topics of BCR-OSCC. RESULTS:Based on existing research reports and the experts' clinical experiences, a consensus on staging, diagnosis, and treatment for BCR-OSCC was formed through extensive discussion. CONCLUSION:This manuscript presents consensus recommendations and a summary of evidence supporting each recommendation. This consensus may improve clinical practices about BCR-OSCC in China and propel more clinical trials to provide high-level evidence for BCR-OSCC management.
The current study aimed to assess the effectiveness of the alveolar bone mucosa- periosteal bone flap technique in horizontally augmenting the alveolar ridge during dental implant placement. This retrospective analysis included 20 patients with a total of 45 implants, and was designed to evaluate the alveolar ridge widths both before and after surgery. Preoperative measurements indicated an average alveolar ridge width of 3.62 ± 0.90 mm, which increased to 6.58 ± 1.16 mm postoperatively. Statistical analysis revealed a significant increase in alveolar ridge width following the procedure (P < 0.05), with an average gain of 2.96 ± 1.21 mm. In summary, these findings suggest that the alveolar bone mucosa-periosteal bone flap technique is an effective approach for widening the alveolar ridge while placing dental implants, meriting its consideration for clinical application.
Background: Periodontitis, a prevalent chronic inflammatory disease, remains a global health challenge with conventional diagnostic methods hindered by subjectivity and low sensitivity. This study aimed to develop a machine learning (ML)-based diagnostic framework using transcriptomic data to enhance diagnostic accuracy and efficiency. Methods: Transcriptomic datasets from 616 samples (452 periodontitis, 164 healthy controls) were retrieved from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified, and functional enrichment, weighted gene co-expression network analysis (WGCNA), and immune infiltration profiling were performed. Key biomarkers were refined using Boruta and Least Absolute Shrinkage and Selection Operator (LASSO) algorithms. Independent six ML models were constructed and validated. A nomogram for risk prediction, transcription factor networks, and drug-target interactions were analysed. Results: Five diagnostic biomarkers (CSF2RB, COL15A1, MME, NEFM, CYP24A1) were identified, with robust performance across datasets. The Random Forest (RF) and eXtreme Gradient Boosting (XGBoost) achieved perfect classification in training and high accuracy in external validation. Immune infiltration analysis revealed significant correlations between biomarkers and immune cell populations (eg, dendritic cells, T cells). Transcription factor networks highlighted NFYA and SP1 as central regulators. Drug prediction identified re-purposable candidates with validated molecular docking affinity. Conclusion: This study establishes a ML-driven diagnostic framework for periodontitis, integrating transcriptomic, immune, and regulatory network insights. These gene biomarkers may provide novel insight into periodontitis pathogenesis, while our diagnostic models show potential for clinical utility in personalised diagnosis, targeted intervention, and therapeutic development. Plain Language Summary: Periodontitis is a common, serious condition often diagnosed too late using traditional methods that can be subjective. To improve detection, we developed an machine learning (ML) tool that analyses genetic activity in gum tissue. Using data from 616 patient samples, we identified five key genes (CSF2RB, COL15A1, MME, NEFM, CYP24A1) that act as biological ‘flags’ for gum disease. These genes are linked to immune responses that drive gum inflammation. Our ML models – especially two types called Random Forest and XGBoost – perfectly spotted gum disease in initial tests and remained highly accurate in new patient groups. We also created a simple scoring chart (nomogram) to predict individual risk. The genes we found interact with immune cells and vitamin D pathways, revealing new disease mechanisms. This work provides a faster, more objective way to diagnose gum disease and opens doors for personalised treatments.
Pearl powder, especially its main effective component water-soluble matrix (WSM), can promote bone formation. The present study analyzed the effect of various WSM concentrations on the osteogenic differentiation of hFOB1.19 cells. The WSM of nanometer pearl powder (NPP) was obtained through the water extraction method. hFOB1.19 cells were then cultured with WSM at concentrations of 0, 10, 20 and 40 µg/ml. Thereafter, alkaline phosphatase (ALP) activity and alizarin red staining were analyzed to detect the effects of WSM on the osteogenic differentiation and mineralization of hFOB1.19 cells. In addition, type I collagen, osteocalcin, osteopontin and Runt-associated transcription factor 2 mRNA and protein expression levels during osteogenic differentiation were measured through reverse transcription-quantitative PCR and western blotting. Following WSM treatment, ALP activity, alizarin red staining of mineralized nodules and osteoblast-related protein expression levels were all found to be elevated in hFOB1.19 cells. In conclusion, these results suggested that NPP WSM could promote the differentiation and mineralization of hFOB1.19 cells within the tested concentration range to induce an osteogenic effect.
Abstract Introduction Oral submucosal fibrosis is a potentially life-threatening oral disease that significantly impacts physiological functions such as speech and swallowing while also diminishing the quality of life for patients. Currently, the mainstream treatment for oral submucosal fibrosis in clinical practice involves invasive glucocorticoid drugs such as injection therapy. However, this method often leads to intraoperative pain, anxiety, fear, and poor medical experience due to associated side effects. Methods There is an urgent need to actively explore new drugs and relatively noninvasive approaches for the treatment of oral submucosal fibrosis in order to enhance patients’ medical experience and compliance. This has become a focal point of attention in clinical research. After conducting an extensive literature search, it was discovered that curcumin, a natural polyphenolic compound, exhibits potent anti-tumor, anti-inflammatory, antioxidant, anti-metastatic and anti-angiogenic properties. Moreover, curcumin holds significant clinical potential in the prevention and treatment of various diseases such as oral submucosal fibrosis. Conclusion This review presents a comprehensive elaboration encompassing the action mechanisms, biological activity, potential applications, and clinical characteristics of curcumin in the management of oral submucosal fibrosis, aiming to provide diagnostic insights and novel therapeutic perspectives for its prevention and treatment.
Abstract Background The present work focused on observing the efficacy of alveolar bone mucosa- periosteal bone flap in alveolar ridge horizontal bone augmentation with dental implant placement. Methods This was a retrospective study involving 49 patients with 99 implants, which was conducted to measure the alveolar ridge widths pre- and post-operatively. The alveolar ridge widths were 4.77 ± 1.49 mm preoperatively and 7.68 ± 1.60 mm postoperatively. Results There was a significant difference in alveolar ridge width before and after operation (P < 0.05), to be specific, the alveolar ridge width increased by 2.91 ± 0.11 mm after operation. Conclusion These results suggest that alveolar bone mucosa-periosteal bone flap technique is an effective method to increase the alveolar ridge width with the simultaneous placement of dental implants, which is worthy to be recommended in clinical practice.
背景:现阶段广泛使用的动物成骨细胞模型的生物学特性与人细胞差距较大;原代人成骨细胞分离培养难提纯、培养代次有限;骨肉瘤细胞有异常生长的风险,都不能完全满足研究需求.1995年,有研究利用猴空泡病毒40转染了人胎儿四肢细胞,筛选得到一组具有分化为较早期成骨祖细胞——永生化人成骨细胞系hFOB1.19.目的:综述hFOB1.19的基本特性、培养方法及作为骨组织工程材料细胞模型的应用.方法:在中国知网、万方数据、SinoMed、PubMed、Web of Science、Medicine及Cochrane Library数据库中查找从1995年至2022年5月的相关文献,中文检索词为"人胎儿成骨细胞系1.19、人成骨细胞系、永生化细胞、猴空泡病毒40、骨组织工程、骨替代材料、生物材料研究",英文检索词为"hFOB1.19,Human osteoblast cell line,Immortalized cells,Monkey vacuolating virus 40,Bone tissue engineering,Bone substitute materials,Biomaterials research",筛选后得到73篇文献进行综述.结果 与结论:①hFOB1.19在形态、表型、核型、生物学特性及分化潜能方面与体内成骨细胞高度相似,拥有快速且稳定的生长能力.②hFOB1.19已广泛应用于细胞黏附、增殖、分化、矿化、基因表达及蛋白合成方面,以检验骨组织工程材料的生物相容性及成骨性能.③hFOB1.19能够弥补动物细胞来源不同、骨肉瘤细胞异常增殖可能、原代成骨细胞分离难及传代次数少的缺点,在骨组织工程实验应用中性能稳定,增殖良好,但因培养条件特殊,细胞传代次数有限及生物安全性等方面的问题,目前在骨组织工程材料领域应用尚且不够广泛.④当前,骨组织工程材料发现速度快,但开发过程中缺乏系统全面的研究体系及统一的研究标准,文章总结hFOB1.19在不同研究中的应用,旨在为研究者们提供方法选择引导并推动相关标准完善.
骨质疏松症是骨代谢异常导致的骨量减少及骨微结构改变,骨脆性增加后继发骨折的一类全身性骨病,近年来已成为影响老年生活质量的主要因素之一.目前,其治疗药物在疗效及长期应用上存在问题,而珍珠层含有成骨活性物质,具有应用于骨质疏松症及其他骨病的潜力.该文就珍珠层活性成分的特点、提取方法及成骨作用研究进展进行综述.
Oral squamous cell carcinoma (OSCC) is a usual oral cancer. Therefore, it's essential to identify targets for its early diagnosis and therapy. This research aimed to explore the roles of human β-defensin-3 (hBD-3) and nuclear factor-kappa B (NF-κB) p65 in the pathogenesis and progression of OSCC. The connection between NF-κB p65 and the carcinogenesis of oral cancer was analyzed by immunohistochemical staining. The relative expressions of hBD-3 and NF-κB p65 in OSCC cells were evaluated by qRT-PCR and Western blot. Afterward, hBD-3 was knocked down, and NF-κB p65 was overexpressed. The cell viability and invasion were tested via CCK-8 and Transwell experiment, and the expression of hBD-3, NF-κB p65, and its downstream molecules was evaluated by Western blot. The expression of NF-κB p65 was increased with the aggravation of the oral submucosal fibrosis. HBD-3 and NF-κB p65 were high-expressed in OSCC cells. The viability and invasion abilities of OSCC cells that knocked down hBD-3 were markedly decreased, while they were restored by the overexpression of NF-κB p65. The expressions of NF-κB p65 and c-myc were diminished while IκB and p21 were raised with the knockdown of hBD-3. After overexpression of NF-κB p65, the expression of hBD-3 and IκB did not change markedly, while c-myc was increased and p21 was decreased dramatically. HBD-3 and NF-κB p65 facilitate the proliferation and invasion of OSCC cells, and hBD-3 may promote this process by governing the expression of NF-κB p65 and its downstream c-myc and p21.
Photodermatology, Photoimmunology & PhotomedicineEarly View LETTER Photodynamic therapy with 20% aminolevulinic acid administered externally in the treatment of oral leukoplakia Yongxiu Du, Yongxiu Du Department of Oral Mucosal Diseases, Hainan Provincial Stomatology Centre, Affiliated Haikou Hospital, Xiangya Medical School, Central South University, Haikou, ChinaSearch for more papers by this authorChenxi Yang, Chenxi Yang Department of Oral Mucosal Diseases, Hainan Provincial Stomatology Centre, Affiliated Haikou Hospital, Xiangya Medical School, Central South University, Haikou, ChinaSearch for more papers by this authorPu Xu, Corresponding Author Pu Xu xupu0128@126.com Department of Oral Implantation, Hainan Provincial Stomatology Centre, Affiliated Haikou Hospital, Xiangya Medical School, Central South University, Haikou, China Correspondence Pu Xu, Department of Oral Implantation, Hainan Provincial Stomatology Centre, Affiliated Haikou Hospital, Xiangya Medical School, Central South University, 43 Renmin Avenue, Meilan District, Haikou, Hainan Province 570208, China. Email: xupu0128@126.comSearch for more papers by this author Yongxiu Du, Yongxiu Du Department of Oral Mucosal Diseases, Hainan Provincial Stomatology Centre, Affiliated Haikou Hospital, Xiangya Medical School, Central South University, Haikou, ChinaSearch for more papers by this authorChenxi Yang, Chenxi Yang Department of Oral Mucosal Diseases, Hainan Provincial Stomatology Centre, Affiliated Haikou Hospital, Xiangya Medical School, Central South University, Haikou, ChinaSearch for more papers by this authorPu Xu, Corresponding Author Pu Xu xupu0128@126.com Department of Oral Implantation, Hainan Provincial Stomatology Centre, Affiliated Haikou Hospital, Xiangya Medical School, Central South University, Haikou, China Correspondence Pu Xu, Department of Oral Implantation, Hainan Provincial Stomatology Centre, Affiliated Haikou Hospital, Xiangya Medical School, Central South University, 43 Renmin Avenue, Meilan District, Haikou, Hainan Province 570208, China. Email: xupu0128@126.comSearch for more papers by this author First published: 11 August 2022 https://doi.org/10.1111/phpp.12828 Yongxiu Du and Chenxi Yang contributed equally to this study and share first authorship. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Early ViewOnline Version of Record before inclusion in an issue RelatedInformation
Background:Oral cancer (OC) is common cancer in the world. Long noncoding RNAs (lncRNAs) have been shown to be involved in cancer regulation, including oral cancer (OC). The aim of this study was to investigate the role of lncRNA deleted in lymphocytic leukemia 2 (DLEU2) in oral cancer.Method:The Gene Expression Omnibus database was used to analyze differentially expressed lncRNA/microRNA (miRNA, miR)/mRNA. The expression levels of DLEU2, miR-30a-5p, and RAP1B in OC cells were detected by RT-qPCR. Dual-luciferase was used to analyze the binding of lncRNA/miRNA/mRNA. Cell Counting Kit-8 was used to measure cell proliferation. Transwell assay was used to inspect cell migration and invasion abilities. Western blot was used to detect MAPK pathway-related protein levels.Result:Our research shows that, in contrast to miR-30a-5p, DLEU2 or RAP1B was upregulated in OC cells, and high expression of DLEU2 or RAP1B was associated with poorer overall survival. Inhibiting the expression of DLEU2 slowed the proliferation and reduced the ability of migration and invasion of Tca8113 and CAL-27 cells. miR-30a-5p was predicted to interact with DLEU2 or RAP1B by bioinformatics, and dual-luciferase analysis confirmed this interaction. Notably, si-DLEU2 suppressed RAP1B expression and protein level, and after overexpression of RAP1B in OC cells, reversal of suppressed DLEU2 expression was observed. Furthermore, the inhibitory effect of si-DLEU2 on MAPK signaling was reversed by overexpression of RAP1B. Therefore, si-DLEU2 regulates MAPK signaling through the miR-30a-5p/RAP1B axis and inhibits OC development.Conclusion:DLEU2 contributed to proliferation, migration and invasion via miR-30a-5p/RAP1B axis to regulate MAPK signaling pathway in OC cells.
浓缩生长因子(concentrated growth factor,CGF)是最新一代自体血液提取物,富含多种生长因子,由纤维蛋白构成三维网络结构.在因龋病、外伤等原因导致牙髓损伤或坏死的牙髓修复与再生治疗中,纤维蛋白可作为支架模拟髓腔内形态,提供三维生物空间结构,维持组织内化学稳定性和机械强度,并给细胞分化、增殖等提供适宜的环境;生长因子具备一定的抗炎及促血管愈合作用,可促进细胞增殖、分化、细胞外基质分泌和矿化等.各组分对牙髓组织修复、再生的影响互不相同,但最终目的是共同促进组织的修复与再生.文章就CGF在牙髓组织修复与再生领域的应用研究进展做一综述.
目的 研究纳米淡水珍珠粉(nanonized freshwater pearl powder,NFPP)对成骨细胞成骨活性的影响.方法 将NF-PP与成骨细胞在体外共同培养,以纳米羟基磷灰石(nanonized hydroxyapatite,NAHA)作为阳性对照组,空白组作为阴性对照组,以细胞贴壁实验检测成骨细胞的黏附,CCK-8法检测成骨细胞的增殖,碱性磷酸酶(alkaline phosphatase,ALP)试剂盒检测成骨细胞的分化,茜素红染色检测成骨细胞矿化结节的形成.结果 成骨细胞的增殖、分化在实验组与两对照组间比较,差异均有统计学意义(P<0.05),但细胞贴壁率实验组与阳性对照组间比较,差异无统计学意义(P>0.05).实验组中矿化结节面积高于两对照组.结论 NFPP能促进成骨细胞的增殖、分化与矿化结节的形成,但对成骨细胞黏附的促进作用与NAHA基本一致.
A nanopearl powder/C-HA (chitosan-hyaluronic acid)/rhBMP-2 (recombinant human bone morphogenetic protein-2) composite artificial bone material was prepared, and its biological properties were evaluated. The nanopearl powder/C-HA/rhBMP-2 composite porous artificial bone material was prepared using the freeze-drying method after the nanopearl powder was prepared using mechanical ball milling. The particle was measured with a transmission electron microscope, its surface morphology and pore size were observed under a scanning electron microscope. The porosity of the artificial bone was determined using pycnometry, a compression performance test was conducted with a universal testing machine, and XRD (X-ray diffraction) patterns were recorded to examine the crystal form of the pearl powder in the composite artificial bone. Finally, the artificial bone was cocultured with mouse MC3T3-E1 cells to investigate its effects on cell proliferation and differentiation and the expression of osteogenesis-related genes. The pearl powder prepared in this experiment had a particle size in the nanometer range. This nanopearl powder, along with C-HA and rhBMP-2, was compounded into the nanopearl powder/C-HA/rhBMP-2 composite artificial bone, showing pore sizes of 188.53 ± 15.32 μm, a porosity of 86.43 ± 2.78% and a compressive strength of 0.342 ± 0.024 MPa. Notably, rhBMP-2 was released from the artificial bone in a sustained manner. Moreover, this artificial bone promoted the adhesion, proliferation, and differentiation of MC3T3-E1 cells and upregulated the expression of ColαI (collagen α1), OCN (osteocalcin), OPN (osteopontin) and Runx2 (runt-related gene 2). Conclusively, this nanopearl powder/C-HA/rhBMP-2 composite artificial bone material showed good performance and cytocompatibility, suggesting that it can be used for bone tissue engineering.
骨细胞外基质是一种细胞黏附、增殖和分化的场所.利用无机非金属材料和可降解聚合物模仿其生理特性和组织结构,改善机械、生物性能,已成为设计和研发支架的一种较为实用的方法.选择性能合适的支架材料相当重要.珍珠粉组成、结构类似天然骨.自Lopez发现以来,学者通过体内与体外研究,证明了珍珠粉具有优于羟基磷灰石的成骨性能和生物相容性,是一种较为理想的无机非金属骨支架材料.它能均匀分散于支架,提供了成骨的主要原料和骨引导的多孔环境,使表面粗糙,从而提高了力学性能和亲水性,也能促进细胞的增殖分化,调节支架的理化和生理学性能. 目前研究较多的为珍珠粉/聚乳酸复合支架以及珍珠粉/壳聚糖-透明质酸复合支架.同时,不少支架已开始载入生长因子提高成骨效果,载入缓释药物探寻抗感染、抗肿瘤的方法,以及使用三维打印令孔隙形状更适合细胞长入和力学性能改善.但种子细胞的研究,元素掺杂的研究,力、电、磁等物理刺激作为组织工程第四元素的研究等,尚少见于珍珠粉复合支架. 本文通过对国内外文献的回顾,对珍珠粉复合支架在骨组织修复的研究进展进行了系统综述.
牙本质敏感症是一种常见、多发的临床症状,具有较高的发生率.研究表明,在18岁~35岁间约有42%的人具有牙本质敏感的症状,50岁以上具有牙本质敏感症状的人为70.8%.目前,治疗牙本质敏感症的主要方法以流体动力理论为基础,采用各种手段来封闭或阻塞暴露的牙本质小管,或封闭牙本质表面以隔绝各种外部刺激,避免小管内液体的异常流动而产生压力变化导致牙髓神经的刺激.然而临床中真正理想的脱敏剂是不存在的,没有一种有效的方法可以达到快速安全、永久性牙本质脱敏的目的.二极管激光是口腔临床常用激光,具有机体小、轻便,造价低廉、治疗波长可调控等优点,已应用于口腔临床多种疾病的治疗.目前,二极管激光已成为治疗牙本质敏感症的一项新技术,并取得了良好的效果,同时经二极管激光照射后牙本质小管管壁粗糙不平,且厚薄不一,容易使药物附着在表面,加速渗透,较单独的使用二极管激光具有更好的封闭效果.本文就国内外有关二极管激光在牙本质敏感症中的治疗及应用的研究进展作一综述.
背景:珍珠中高含量的钙离子可以促进钙盐沉积,抑制破骨细胞的骨吸收活性,促进骨再生,且其含有的水溶性蛋白具有骨诱导作用,可促进成骨细胞的分化.目的:观察纳米淡水珍珠粉对成骨细胞成骨相关基因表达的影响.方法:取第3代小鼠成骨细胞MC3T3-E1细胞,分别与纳米淡水珍珠粉(实验组)、纳米羟基磷灰石(对照组)共培养,以单独培养的细胞为阴性对照.培养7 d后,采用RT-PCR实验检测各组Runx2、骨桥蛋白、Ⅰ型胶原mRNA的表达.结果 与结论:①实验组、对照组Runx2与骨桥蛋白mRNA表达量高于阴性对照组(P<0.05),并且实验组Runx2与骨桥蛋白mRNA表达量高于对照组(P<0.05);②实验组Ⅰ型胶原mRNA表达量高于对照组、阴性对照组(P<0.05),对照组与阴性对照组Ⅰ型胶原mRNA表达量比较差异无显著性意义(P>0.05);③结果 表明,纳米淡水珍珠粉较纳米羟基磷灰石更能显著促进成骨相关基因Runx2、骨桥蛋白、Ⅰ型胶原mRNA的表达.