骨形态发生蛋白-7(BMP-7)在骨骼系统中的作用

探讨骨形态发生蛋白－７在骨骼系统不同发育时期、不同细胞和疾病中的作用。方法：广泛查阅近期有关ＢＭＰ－７在骨骼系统中不同作用的文献,综述有关内容。结果：ＢＭＰ－具有强烈的骨诱导活性,可在异位诱导新骨形成;在骨骼发育的不同阶段具有一定的调节作用;它可促进成骨细胞增殖和碱性磷酸酶的表达,并促进软骨细胞蛋白我糖表达和关节软骨缺损的修复;ＢＭＰ－７在黄韧带骨化和后纵韧带骨化等疾病的发生方面具有一定的促进作用     

PRP/脱蛋白异种骨修复兔桡骨骨缺损的组织学研究

目的探讨富血小板血浆(platelet-rich plasma,PRP)和脱蛋白牛松质骨复合物修复节段性骨缺损的疗效。方法新西兰大白兔28只,切除兔桡骨中下段1 cm的骨质,其中空白组骨缺损区不作处理,试验组骨缺损区植入PRP 脱蛋白牛松质骨,对照组骨缺损区单纯植入脱蛋白牛松质骨。于术后第2、4、8、12周分别处死7只试验动物,结果按Lane骨移植组织学评分标准评分,并进行图像分析,测其新生骨面积。结果术后实验组Lane骨移植组织学评分高于对照组,实验组新生骨面积明显高于对照组。结论复PRP异种脱蛋白骨可用于节段性骨缺损的修复,在骨缺损的修复中具有促进作用成骨方式为骨传导和骨诱导。     

雌激素对骨折愈合过程中骨形态发生蛋白4 mRNA表达的影响

目的：探讨骨折愈合过程中雌激素对骨形态发生蛋白4(bone morphogenetic protein-4，BMP—4)基因表达的影响，了解BMP—4在骨折愈合过程中的作用。方法：180只雌性SD大鼠随机分成4组。OVXE1组为卵巢切除后1d开始雌激素替代治疗；OVXE2组为骨折后雌激素替代组；OVX组为雌激素缺乏组；SO组为正常对照组。所有动物在一侧胫骨中段造成骨折模型；各组动物分别在骨折后1、2、3、4、5、6、7、14、28d处死取材；标本制成石蜡切片，用地高辛标记的BMP-4 cDNA探针进行原位核酸分子杂交；实验结果经计算机图像处理系统分析并作统计学处理。结果：各组动物骨折后1—3d，骨折周围血肿及组织内BMP—4 cRMA检测为阳性，从第4d开始为阴性。OVX组的BMP—4 mRNA表达较任何一组都明显增多(P＜0．05)；SO组及OVXE1组最少。结论：BMP—4主要在骨折愈合早期起作用。雌激素对BMP-4基因的表达有抑制作用，将BMP—4基因的表达控制在一定程度内可能是雌激素调节骨折愈合的一种方式。     

复合骨形态发生蛋白胎儿骨修复长骨缺损的实验研究

寻找满意的骨形态发生蛋白（ＢＭＰ）的载体一直是应用ＢＭＰ修复骨缺损研究中的一个重要课题，为探讨胎儿骨（ＦＢ）能否成为ＢＭＰ载体，制备了复合ＢＭＰ胎儿骨（ＢＭＰ／ＦＢ），将其植入兔桡骨中段１５ｍｍ人工缺损处，以单纯ＦＢ植入、异体骨（ＡＬＢ）植入、空白作为对照，通过Ｘ线摄片，光镜观察，电子探针钙磷元素测定等方法了解各组骨缺损修复速度和愈合程度。结果发现ＢＭＰ／ＦＢ植入侧４周时骨缺损处有大量间充质细胞聚集，８周形成骨小梁，ＦＢ基本被吸收，１２周出现部分板层骨，钙磷值达到正常桡骨皮质骨水平，１６周骨细胞成熟，髓腔再通，外观塑形较好，在不同时间点骨缺损修复程度，ＢＭＰ／ＦＢ组明显优于ＦＢ组，ＦＢ组优于ＡＬＢ组，空白组骨缺损则被纤维组织，脂肪组织等填充。实验证明ＦＢ是一种良好的ＢＭＰ载体。     

BMP-2基因转染对人成纤维细胞生长和增殖的影响

目的：研究人骨形态发生蛋白-2(BMP-2)基因转染对人成纤维细胞株KMB-17生长及增殖的影响。方法：将hBMP-2基因导入KMB-17细胞，检测其表达情况及对KMB-17细胞生长和增殖的影响。结果：KMB-17细胞至少可以表达BMP-2基因3周左右；并且增殖指数上升，细胞增殖加剧。结论：人成纤维细胞株KMB-17可以作为靶细胞用于BMP-2基因疗法研究。     

四种可溶性载体对骨形态发生蛋白在小鼠体内诱导成骨活性的影响

以四种可溶性物质作为牛骨形态发生蛋白（ｂＢＭＰ）的载体，通过实验观察哪种物质是ｂＢＭＰ的有效缓释载体。将聚乙烯吡咯烷酮（ＰＶＰ）、葡聚糖、羟乙基淀粉（ＨＥＳ）、甘露醇分别与等量ｂＢＭＰ复合后，注射入小鼠股部肌肉，观察组织学成骨及测定标本内钙含量。结果，ｂＢＭＰ／ＰＶＰ有良好成骨，吸收较快，未见炎症及排斥反应，其混悬液较稳定，具有良好的适针性及可注射性，ｂＢＭＰ／甘露醇只有很低成骨率。其余各组未见成骨。ＰＶＰ对ｂＢＭＰ具有满意助溶、助悬及缓释载体作用，对ｂＢＭＰ活性无损害，生物相容性好。     

富血小板血浆重组脱蛋白异种骨修复兔桡骨骨缺损的放射学评估

目的从放射学方面来评价富血小板血浆重组脱蛋白异种骨修复节段性骨缺损的疗效。方法新西兰大白兔28只,采用二次离心法制成PRP,将PRP与激活剂按5：1比例制成PRP凝胶。在右桡骨中下段造一长1 cm的骨缺损,随机分空白组、实验组、对照组。术后第2、4、8、12周分别对3组家兔行尺桡骨X线检查,根据Lane骨移植X线片评分了解两侧桡骨骨缺损区修复情况。结果术后伤口愈合良好,实验侧Lane骨移植X线片评分明显高于对照侧。结论复PRP异种脱蛋白骨可用于节段性骨缺损的修复,动物卖验证明PRP在骨缺损的修复中具有促进作用。     

BMP-2基因转染的人骨髓基质干细胞复合PLA/PCL支架体外构建组织工程骨

目的　用人骨形态发生蛋白 2腺病毒表达载体 (Ad -BMP - 2 )转染的人骨髓基质干细胞 (hBMSC) ,复合PLA/PCL(聚乳酸 /聚己内酯 )生物降解支架体外构建组织工程骨。方法　用Ad -BMP - 2转染体外培养的成人BMSC ,免疫组化、原位杂交染色和蛋白印迹方法检测细胞BMP - 2的表达 ,并通过流式细胞仪和ALP活性检测分析其对细胞增殖、分化的影响。然后将转染后细胞接种到PLA/PCL支架上 ,扫描电镜观察细胞贴附、生长状况。结果　转染后 ,hBMP - 2基因在mRNA水平和蛋白水平均有表达 ;S期细胞比例和ALP活性明显增高。扫描电镜见转染细胞分布均匀 ,伸展良好。结论　Ad-BMP - 2可高效转染hBMSC ,且促进细胞增殖及成骨转化。转染后细胞在PLA/PCL上生长良好 ,BMP - 2基因治疗的组织工程骨构建成功     

Use of Platelet Rich Plasma for the Treatment of Bicipital Tendinopathy in Spinal Cord Injury:: A Pilot Study

The purpose of study is to explore the efficacy and safety of platelet rich plasma (PRP) in the nonoperative management of shoulder tendinopathy amongst individuals with spinal cord injury. This objective was met by completing a pilot study on the effectiveness and safety of a PRP injection into the biceps tendon demonstrating clinical and ultrasonagraphic pathology. Recent analysis of the preliminary pilot data has demonstrated remarkably convincing results demonstrating both the safety and efficacy of this novel intervention.     

Evidence for the use of PRP in chronic midsubstance Achilles tendinopathy: A systematic review with meta-analysis

BackgroundPlatelet-rich plasma (PRP) injections have been proposed as an additional therapy in the treatment of chronic midsubstance Achilles tendinopathy (AT). The use of PRP injections as pharmacological treatment added to a conservative approach has gained growing interest, but the efficacy remains highly debated. The varying methodological quality of the available studies may contribute to these contradictory results. The aim of this systematic review with meta-analysis was to establish the existing evidence of PRP injections for chronic midsubstance AT on the functional outcome, with a risk of bias assessment of each included study.MethodsAccording to the PRISMA guidelines systematic searches were performed in Embase, the Cochrane library and Pubmed on June 12, 2020 for relevant literature. Only clinical trials comparing PRP injections with placebo, additional to an eccentric training program, in midsubstance AT were included. The primary outcome was Victorian Institute of Sport Assessment - Achilles (VISA-A) score at 3, 6 and 12 months post-injection. Risk of bias was assessed using the Cochrane risk-of-bias tool for randomized trials (Rob 2). As secondary outcome we assessed reported changes in tendon structure after PRP injections.ResultsA total of 367 studies were identified with the initial database search. Finally, four randomized controlled trials (RCTs) met inclusion criteria for systematic review and meta-analysis with data of 170 patients available for pooling. Results showed no difference in clinical outcome between the PRP and placebo group at different points in time using the VISA-A score as outcome parameter (3 months 0.23 (CI -0.45, 0.91); 6 months 0.83 (CI -0.26, 1.92); 12 months 0.83 (CI -0.77, 2.44)). The bias analysis showed a low or intermediate risk of bias profile for all studies which supports the good methodological quality of each included article. Finally, it is unclear whether PRP injections cause an improvement in tendon structure. However, no direct relationship between tendon structure and clinical presentation of AT could be found.ConclusionPRP has no clear additional value in management of chronic midsubstance Achilles tendinopathy and therefore should not be used as a first-line treatment option.     

Bone Morphogenetic Protein-2 Stimulates Differentiation of Cultured Spinal Ligament Cells from Patients with Ossification of the Posterior Longitudinal Ligament

Ossification of the posterior longitudinal ligament (OPLL) of the spine is characterized by heterotopic bone formation occurring in spinal ligament, causing severe compression myelopathy. In order to investigate the mechanism of OPLL development, we isolated spinal ligament cells from OPLL patients as well as non-OPLL patients, and established 10 OPLL cell lines and 7 non-OPLL cell lines, respectively. We analyzed the effects of bone morphogenetic protein-2 (BMP-2) on these cells with respect to alkaline phosphatase (AP) activity, DNA synthesis, and collagen production. BMP-2 caused a significant increase of AP activity in 4 OPLL cell lines, whereas the activity did not change in any non-OPLL cells. Among OPLL cells, BMP-2 stimulated DNA synthesis in four cell lines and procollagen type I carboxyl-terminal peptide (PICP) synthesis in five cell lines. Some non-OPLL cells also responded to BMP-2, as there was an increase of DNA synthesis in three cell lines and PICP synthesis in one cell line. These data collectively indicate that BMP-2 preferentially induces osteogenic differentiation in OPLL cells rather than in non-OPLL cells. OPLL cells, therefore, exhibit a different response to BMP-2 than non-OPLL cells, suggesting that the expression of BMP receptor(s) and/or the signal transduction initiated by BMP-2 in the spinal ligament cells of OPLL patients somewhat deviate from those in normal spinal ligament cells. Such abnormal characteristics of OPLL cells as described here provide some clues to the clarification of the pathogenesis of OPLL. Received: 1 April 1996 / Accepted: 19 July 1996     

两种内固定后兔骨痂中成骨细胞内骨形态生成蛋白含量的比较

目的：比较钢板和矩形髓内钉固定对兔胫腓骨骨折成骨细胞内骨形态生成蛋白（BMP）含量的影响。方法：新西兰兔24只，对同一动物的两侧胫骨分别用矩形髓内钉和4孔不锈钢钢板固定，并分3批于固定后14、21、28d处死。用兔疫组化方法检测骨痂中成骨细胞中BMP的分布，用计算机图像分析系统将结果进行定量分析。结果：矩形髓内钉组骨痂中成骨细胞内BMP含量高于钢板组（P＜0．05）。结论：矩形髓内钉内固定胫骨后骨痂含量增加可能与矩形髓内钉的微动有关，可能有利于骨折愈合。     

髓芯减压联合自体骨髓基质干细胞移植治疗兔激素性股骨头坏死实验研究

目的探讨髓芯减压联合自体骨髓基质干细胞(BMSC)移植对兔激素性股骨头坏死的治疗作用。方法建立早期激素性股骨头坏死动物模型后,随机分为三组,A 组为右侧髓芯减压组(10 只);B 组为右侧髓芯减压结合自体 BMSC 移植组(10 只);C 组为未治疗组(12 只)。 A、B、C 组都于使用激素后的第 12 周处死,所获股骨头标本组织切片行 HE 染色观察。分别在建模前,治疗前,治疗后采外周血化验凝血酶原时间(PT)、纤维蛋白原(Fib)、总胆固醇(TC)、甘油三酯(TG)。结果建立模型动物死亡率为 8.6%(3/35)。 A、B、C 组右侧股骨头坏死率分别为 50%(5/10)、20%(2/10)、75%(9/12)。 B 组与 A 组、C 组相比空骨陷窝率下降、骨髓坏死面积减少、骨小梁体积比增加(P0.05)。使用激素后 Fib 下降,PT、TC、TG 升高(P0.05),自体 BMSC 移植后这些结果恢复接近正常范围。结论髓芯减压联合自体骨髓基质干细胞移植对兔早期激素性股骨头坏死有治疗作用。     

四种载体吸附自体骨髓细胞移植成骨作用的实验研究

目的　比较骨基质海绵 ,羟基磷灰石 ,明胶海绵及海螵蛸结合自体骨髓细胞在兔肌肉中的成骨作用。方法　应用骨基质海绵 ,羟基磷灰石 ,明胶海绵及海螵蛸结合自体骨髓细胞经过孵育后 ,植入兔股部肌肉内 ,分别于不同时间通过X线及组织学观察 ,计算机图像分析 ,评价各不同组织的成骨情况。结果　 12周时 ,骨基质海绵组成骨能力最强 ,羟基磷灰石组次之 ,海螵蛸组成骨能力最弱 ,明胶海绵组无成骨能力。结论　骨基质海绵吸附自体骨髓是修复骨折及骨缺损的较好材料。     

富血小板血浆联合关节镜松解治疗冻结肩的疗效分析

目的 评估富血小板血浆（platelet-rich plasma,PRP）联合关节镜松解治疗冻结肩的疗效。方法 回顾性分析2019年1月至2022年12月我科收治的40例采用关节镜松解治疗冻结肩的病人,根据术后注射药物的不同,分为PRP组（20例）和曲安奈德组（20例）,记录并比较两组病人术前、术后1个月、术后3个月、术后6个月、术后12个月的疼痛视觉模拟量表（VAS）评分、Constant-Murley肩关节功能评分以及肩关节主动前屈、外展、外旋的活动度。结果 与术前相比,两组病人术后各观察时间点的VAS评分显著降低,Constant-Murley评分显著升高,差异有统计学意义（P＜0.05）。术后6、12个月时,PRP组病人的Constant-Murley评分显著高于曲安奈德组;术后12个月时,PRP组在主动前屈、主动外展、主动外旋活动度方面均要优于曲安奈德组,差异有统计学意义（P＜0.05）。结论 PRP联合关节镜松解能有效缓解冻结肩病人的疼痛,改善肩关节的功能,是一种有效的治疗方案。     

Comparison of Osteogenic Potentials of BMP4 Transduced Stem Cells from Autologous Bone Marrow and Fat Tissue in a Rabbit Model of Calvarial Defects

We compared bone marrow stem cells (BMSCs) and adipose-derived stem cells (ADSCs) of adult rabbits under identical conditions in terms of their culture characteristics, proliferation capacity, osteogenic differentiation potentials induced by adenovirus-containing bone morphogenetic protein 4 (Ad-BMP4) in vitro, and capacity to repair calvarial defects in the rabbit model by autologous transplantation ex vivo. According to the results of growth curve, cell cycle, and telomerase activity analysis, ADSCs possess a higher proliferation potential. Both of the Ad-BMP4 transduced MSCs expressed BMP4 mRNA and protein and underwent osteogenic differentiation. Up-regulated mRNA expression of all osteogenic genes was observed in differentiated BMSCs and ADSCs, but with different patterns confirmed by real-time RT-PCR. Deposition of calcified extracellular matrix was significantly greater in differentiated ADSCs compared with differentiated BMSCs. X-ray and histological examination indicated significant bone regeneration in the calvarial defects transplanted with Ad-BMP4 transduced autologous MSCs compared to the control groups. There was no significant difference in new bone formation in Ad-BMP4 transduced MSCs based on quantitative digital analysis of histological sections. The use of ADSCs often resulted in the growth of fat tissue structures in the control groups, and the fat tissue structures were not seen with BMSC cells. Our data demonstrate that BMP4 can be potently osteoinductive in vivo, resulting in bone repair. ADSCs may be an attractive alternative to BMSCs for bone tissue engineering under appropriate stimuli. But the easy adipogenic differentiation needs to be considered when choosing adipose tissue for specific clinical application.     

骨髓间充质干细胞自体移植治疗心肌梗死的实验研究

目的探讨兔骨髓间充质干细胞(MSCs)移植至缺血心肌后的增殖分化情况,对缺血心肌细胞的修复重建能力及心功能改善情况。方法将20只新西兰白兔随机分为骨髓间充质干细胞移植组(MSCs组,n=10)和对照组(n=10),采用结扎冠状动脉左前降支(LAD)制备心肌梗死模型,2周后分别将Dil标记的1×106个细胞悬液400μl或等量L-DMEM培养基用微量注射器注入梗死灶边缘,于建模前、建模后2周、细胞移植后2、4周采用多普勒超声心动图检测左心室收缩期末内径(LVESD)、左心室舒张期末内径(LVEDD),计算左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)评价心脏收缩功能,同时进行心肌声学造影评价心肌组织的血流灌注情况。细胞移植后8周处死所有动物,病理学检查移植细胞在梗死区的生长状况。结果多普勒超声心动图检测结果显示:两组动物建模前、建模后2周LVEF、LVFS差异无统计学意义(0.72±0.08vs.0.71±0.04,0.56±0.11vs.0.55±0.09;0.35±0.06vs.0.35±0.04,0.24±0.08vs.0.23±0.03,P>0.05),细胞移植后2、4周MSCs组LVEF、LVFS值均明显高于对照组(0.71±0.05vs.0.60±0.05,0.72±0.07vs.0.62±0.08;0.34±0.03vs.0.29±0.01,0.35±0.06vs.0.27±0.05,P<0.05);病理学检查见自体MSCs移植8周后存活于梗死心肌中,表达肌细胞特异性标志,并且能显著增加瘢痕区毛细血管密度(38.6±7.6/mm2vs.21.4±3.9/mm2,P<0.05),心肌声学造影亦显示梗死局部血流灌注MSCs组较对照组明显改善。结论自体MSCs移植缺血心肌中可向心肌细胞分化,增加心肌血流灌注,改善心脏收缩功能。