前交叉韧带切断诱导兔膝骨性关节炎模型:阿仑膦酸钠与盐酸氨基葡萄糖对其关节软骨和软骨下骨的保护作用

背景:氨基葡萄糖是骨关节炎特异性的治疗药物,有研究表明骨吸收抑制剂阿伦膦酸钠对骨性关节炎具有潜在的治疗作用。目的:探讨阿仑膦酸钠联合盐酸氨基葡萄糖对前交叉韧带切断诱导的兔膝骨性关节炎模型关节软骨和软骨下骨的保护作用及其作用机制。方法:将3月龄新西兰大白兔随机分为假手术组,模型组,盐酸氨基葡萄糖组,联合治疗组。除假手术组外,其余3组动物均右侧膝关节行前交叉韧带切断建立兔膝骨性关节炎模型。建模成功后,模型组用生理盐水治疗;盐酸氨基葡萄糖组给予盐酸氨基葡萄糖灌胃;联合治疗组给予盐酸氨基葡萄糖组灌胃同时,皮下注射阿仑膦酸钠。8周后观察膝关节外观,取所有组兔胫骨去除软骨后行软骨下骨生物力学检测,测定最大载荷和弹性模量,取股骨测量远端1/4骨密度后,用苏木精-伊红染色及"Mankin评分"观察关节软骨退变情况。结果与结论:建模后盐酸氨基葡萄糖组和联合治疗组膝关节出现了轻度骨性关节炎的表现。盐酸氨基葡萄糖组和联合治疗组Mankin评分显著低(P0.05)。联合治疗组股骨远端骨矿物质密度最高(P0.05)。盐酸氨基葡萄糖组的最大载荷和弹性模量均显著低于联合治疗组(P0.05)。实验结果提示,阿仑膦酸钠与盐酸氨基葡萄糖组联合应用可通过保护关节软骨及改善软骨下骨代谢的双重作用,抑制前交叉韧带切断术后兔膝骨性关节炎的发展,且效果优于单纯用盐酸氨基葡萄糖治疗。     

膝关节神经支选择性切断对膝骨性关节炎模型兔关节软骨Ⅱ型胶原的影响

目的观察选择性切断膝关节神经支对膝骨性关节炎模型兔关节软骨Ⅱ型胶原影响。方法采用改良Hulth法复制兔膝骨性关节炎模型,通过外科显微镜下选择性切断兔膝关节神经支。兔膝关节软骨组织切片HE染色,光镜下观察关节软骨组织结构;免疫组织化学检测软骨Ⅱ型胶原表达。结果模型组和治疗组关节软骨Ⅱ型胶原表达,在术后4周高于正常组;术后16周,明显低于正常组。治疗组术后16周软骨Ⅱ型胶原表达明显高于模型组。结论选择性切断膝关节神经支能增加膝骨性关节炎模型兔关节软骨Ⅱ型胶原的表达。     

软骨下骨量变化与软骨退变的相关性

背景：关节软骨与软骨下骨在骨关节炎病变进程中的相互作用机制目前尚未完全阐明。软骨下骨量改变在骨关节炎病理进程中亦发挥重要作用。 目的：分析2种手术方式及2种蛋白酶诱导建立兔膝关节骨关节炎动物模型的效果,以及软骨下骨量变化与关节软骨退变的相关性。 方法：32只新西兰大白兔随机分为4组：Hulth模型组、前交叉韧带切断模型组、Ⅱ型胶原蛋白酶组及木瓜蛋白酶组,每组8只,右膝关节造模,左膝关节作为自身对照。造模后0,4,8周行DXA扫描,8周行MRI扫描后处死实验动物,取双侧膝关节制作病理组织学切片,比较各组膝关节影像学表现、大体形态及病理变化,并采用Mankin评分进行定量分析。 结果与结论：造模后0,4,8周实验侧膝关节骨密度进行性降低,骨量降低程度Hulth模型组>前交叉韧带切断模型组>Ⅱ型胶原蛋白酶组>木瓜蛋白酶组。MRI显示实验侧股骨内外髁关节软骨厚度变薄,厚度Hulth模型组<前交叉韧带切断模型组<Ⅱ型胶原蛋白酶组<木瓜蛋白酶组。大体标本、组织切片观察及Mankin评分显示手术建模组骨关节炎程度较药物组重,Hulth模型组病变最重,木瓜蛋白酶组最轻。结果说明关节内手术及关节腔内注射蛋白酶均能建立骨关节炎动物模型;手术造模可复制出中晚期骨关节炎,药物诱导可产生骨关节炎早期改变。骨关节炎病变严重程度与软骨下骨骨密度呈负相关;关节软骨退变和软骨下骨改变相互关联,病变进行性发展。     

以关节不稳建立的大鼠骨关节炎模型

背景：骨性关节炎是一种复杂的多病因退变性关节疾病。早期进行骨性关节炎的防治尤其重要。但获取足量的适合研究的早期骨性关节炎的人类骨标本十分困难。 目的：观察关节不稳方法建立骨关节炎模型大鼠的关节软骨组织学变化。 方法：10周龄雄性SD大鼠随机分为2组：实验组切除右膝内侧半月板及内侧副韧带,对照组仅切开关节囊。于术后1,2,4,6,8周取右膝关节标本,行病理组织学检查分析大鼠骨关节炎病程的变化情况。 结果与结论：①术后2,4,6,8周,实验组关节软骨退变程度呈现轻度糜烂、溃疡磨损、严重磨损、骨赘形成等病理变化。②术后1,2,4,6,8周,实验组关节软骨评分均明显高于对照组(P < 0.05)。结果显示该实验采用内侧副韧带切断+内侧半月板切除方法成功建立了大鼠膝关节骨关节炎模型,且造模后4周内的病理、形态学改变类似于人类早期膝关节骨关节炎表现,是研究早期骨关节炎的理想模型。     

可注射性纤维蛋白凝胶/脱钙骨基质复合支架延缓兔骨关节炎软骨退变

背景:纤维蛋白凝胶及脱钙骨基质都有优良的生物相容性及生物降解性,因此可以作为软骨组织工程支架培养软骨种子细胞。这两种材料分别可以作为生长因子的载体缓慢释放生长因子,并达到持续发挥促软骨细胞生长的功能。目的:验证可注射性纤维蛋白凝胶/脱钙骨基质复合支架延缓骨性关节炎的可行性及有效性。方法:实验为同体对照动物实验。16只兔切断双后肢前交叉韧带制备兔膝关节骨性关节炎模型,兔一侧膝关节内注射复合支架材料与软骨细胞混悬液为实验组。另一侧膝关节内注射等量生理盐水为对照组,12周后取关节软骨,分别进行苏木精-伊红染色,Masson染色,Ⅱ型胶原免疫组化染色,并根据Wakitani标准及Outerbridge分类重新制定标准进行评分,评价实验组与对照组软骨退变的程度。结果与结论:实验组关节软骨表面尚光滑,可见软骨陷窝,结构软骨退变较对照组轻;软骨细胞及Ⅱ型胶原较正常软骨组织轻度减少,关节囊组织无明显Ⅱ型胶原表达。实验组综合评分低于对照组(P0.01)。表明可注射性纤维蛋白凝胶/脱钙骨基质复合支架为早期骨性关节炎及骨缺损修复提供了一种优良的复合支架材料。     

维骨力预防骨关节炎软骨退变的实验研究

目的:观察维骨力(viartrils)对兔实验性早中期骨关节炎(OA)病变发生发展是否有预防作用及其对OA软骨细胞增殖的影响。方法:24只新西兰兔用切断膝关节前、后交叉韧带的方法复制兔OA模型,随机分为对照组和实验组各12只,实验组术后即加服维骨力(主要成份为硫酸氨基葡萄糖)每天2粒,对照组常规饲养。术后第10周处死动物,取股骨髁负重面软骨标本进行HE、safranin’O/fast green组织化学染色及骨关节炎评分、分级,采用免疫组化方法观察软骨细胞增殖状况。结果:切断兔前后交叉韧带成功复制出OA早、中期模型,第10周时实验组(维骨力组)骨关节炎病理评分显著低于对照组(P<0.05),软骨细胞增殖指数显著高于对照组(P<0.05)。结论:维骨力对兔膝骨关节炎软骨细胞有刺激增殖的作用,可以较好地预防OA的发生发展。     

常山酮阻止早期骨性关节炎的关节软骨退变北大核心

背景:研究证实,常山酮能够减弱骨性关节炎病程发展的进程。目的:进一步验证常山酮对早期骨性关节炎的防治作用。方法:健康C57BL6J雄性小鼠45只,随机分为3组,每组15只,假手术组只打开小鼠右膝关节囊不损伤其他部位,术后不做处理;其余小鼠均切断小鼠右膝前交叉韧带造骨性关节炎模型,安慰剂组造模后第3天开始给予蒸馏水灌胃每天1次;常山酮组造模后第3天开始按0.5 mg/kg剂量灌胃,每天1次,28 d后处死小鼠取右膝关节,做苏木精-伊红染色和番红固绿染色观察关节组织的形态和结构;免疫组织化学检测转化生长因子β1的表达量。结果与结论:(1)组织学观察,假手术组关节软骨结构正常,潮线清晰,细胞排列整齐,未有软骨表面磨损痕迹;安慰剂组关节软骨层明显变薄,甚至部分损伤至潮线,软骨表面磨损严重并有碎裂现象,细胞排列紊乱;常山酮组软骨细胞分层较清晰且排列较整齐,潮线清晰,细胞形态较规则;(2)3组透明软骨厚度假手术组>山酮组>安慰剂组,钙化软骨厚度假手术组<常山酮组<安慰剂组,透明软骨厚度/钙化软骨假手术组>常山酮组>安慰剂组;(3)OARSI评分常山酮组显著低于安慰剂组,转化生长因子β1阳性细胞/软骨细胞值常山酮组显著低于安慰剂组,2项指标3组间比较差异均有显著性意义(P<0.05);(4)结果表明,常山酮灌胃能部分阻止小鼠早期骨性关节炎关节软骨退变,其作用机制可能是降低转化生长因子β1的表达,从而延缓骨性关节炎的进展。     

膝关节神经支选择性切断对膝骨性关节炎模型兔关节软骨病理变化的影响

目的:观察选择性切断膝关节神经支对膝骨性关节炎模型兔关节软骨病变的影响。方法:采用改良Hulth法复制兔膝骨性关节炎模型,通过外科显微镜下选择性切断兔膝关节神经支。利用"测定双足平衡设备"检测和评价兔膝关节功能变化,肉眼观察兔膝关节大体结构。组织切片H-E染色,光镜下观察关节软骨组织结构,应用显微电脑测量软件测量关节软骨厚度。运用TUNEL法检测软骨细胞的凋亡。结果:模型组右侧(患侧)膝关节蜷缩、无力,检测显示以左侧后足承重为主。治疗组右侧(患侧)后足承重分布情况较模型组有明显改善。模型组兔膝关节软骨出现退变的表现,软骨细胞过度凋亡,其凋亡指数明显高于正常组,而治疗组兔膝关节软骨退变有明显改善,细胞凋亡指数明显低于模型组。模型组和治疗组膝关节软骨厚度均较正常组有明显减小,但治疗组软骨厚度较模型组有明显增厚。结论;选择性切断膝关节神经支对膝骨性关节炎模型兔关节软骨细胞凋亡有抑制作用,并能改善病变关节软骨的结构,加强关节的功能。     

兔膝关节神经支选择性切断后对关节软骨的影响

目的观察兔膝关节神经支选择性切断后关节软骨形态学变化。方法在外科显微镜下选择性切断兔膝关节神经支,术后4、8、16周取材,肉眼观察兔膝关节大体结构,组织切片HE染色,光镜下观察关节软骨组织结构,应用显微电脑测量软件测量关节软骨厚度。结果对照组兔膝关节软骨表面光滑,软骨细胞呈四层结构排列,软骨细胞为圆形或椭圆形,表层呈梭形。实验组兔膝关节软骨组织结构未见明显改变,软骨厚度与对照组比较差异无统计学意义(P0.05)。结论选择性切断兔膝关节神经支对关节软骨组织结构无明显影响,膝关节局部去神经化术治疗具有可行性。     

强力霉素对兔骨关节炎软骨组织形态的影响

目的研究口服强力霉素对兔骨关节炎软骨组织形态的影响及其机制。方法30只日本大耳白兔随机平分为对照组(假手术组)、模型组和治疗组。对照组只行右膝关节切开术,模型组和治疗组行右前交叉韧带切断术,以建立兔膝关节炎模型。术后4周起,治疗组每日给予口服强力霉素1次(4 mg/kg),共5周,观察指标包括软骨大体形态,软骨Mankin评分,关节液中NO含量。结果强力霉素治疗组软骨面退变明显轻于模型组,Mankin评分和NO含量亦显著降低。结论口服强力霉素对兔骨关节炎软骨退变有明显的治疗作用,其机制与抑制NO产生有关。     

Enhancement of subchondral bone quality by alendronate administration for the reduction of cartilage degeneration in the early phase of experimental osteoarthritis

To evaluate the effects of alendronate (ALN) on the subchondral bone quality and cartilage degeneration in the early phase of experimental model of osteoarthritis after anterior cruciate ligament transaction (ACLT). Thirty male adult healthy Japanese white rabbits after right ACLT or sham operation were divided into three groups (n = 10 per group): Sham; ACLT + ALN [after ACLT, the rabbits were treated with ALN daily starting from 4 days after surgery (10 μg/kg/d subcutaneously)]; and ACLT + NS group (after ACLT, the rabbits were injected saline as a placebo). At 60 days postsurgery, specimens from the affected knees were harvested. Histological analysis (HE and Safranin-O staining) as well as Mankin score were carried out to assess the cartilage degradation. BMP-2 and MMP-13 immunohistochemistry were also performed to demonstrate the alterations of cartilage molecular metabolism. Subchondral bone quality was evaluated by bone mineral density (BMD) and microstructure histomorphometry assay. For bone mineral density evaluation, 1/4 distal femurs, medial and lateral regions of femoral condylus were scanned with dual X-ray absorptiometry to assess the subchondral bone mass. Giemsa, von Kossa stain, and fluorescence technique for undecalcified bone section were carried out to examine the morphometry of the subchondral trabecular bone and subchondral plate. Histological and Mankin score analyses displayed that ALN treatment markedly reduced cartilage lesions and delayed the cartilage degeneration in OA joints. Immunohistochemistry assay further indicated that this cartilage-protective role of ALN was associated with elevating BMP-2 while inhibiting MMP-13 expression. BMD assessment demonstrated that ALN treatment significantly suppressed subchondral bone resorption. The results from histomorphometry assay of subchondral bone revealed that ALN treatment markedly increased the percent trabecular area (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N). Moreover, both thickness and the porosity of the subchondral plate in ACLT + ALN group presented significantly higher than that in ACLT + NS group, while no significant difference was found between ACLT + ALN and Sham group. ALN plays an important role in cartilage protection in OA joints that is associated with the improvement of subchondral bone quality through reduction of subchondral bone resorption. ALN could be potentially used as a disease-modifying strategy to limit the progression of OA.     

脱钙骨基质与骨髓间充质干细胞共培养关节腔内的成软骨活性

背景：将骨髓间充质干细胞附着到支架材料上再植入关节软骨缺损处,细胞不但不消失,而且可形成新的软骨。 目的：观察同种异体脱钙骨基质与骨髓间充质干细胞共培养在关节内的成软骨活性。 方法：在54只青紫蓝兔单侧膝关节制作关节软骨全层缺损模型,随机分组：实验组在缺损处植入自体骨髓间充质干细胞与同种异体脱钙骨基质复合物,对照组缺损处仅植入同种异体脱钙骨基质,空白对照组未植入任何物质。 结果与结论：植入后12周,实验组缺损处修复组织呈软骨样,表面光滑平坦,与周围软骨整合的软骨细胞更为成熟,修复组织与软骨下骨结合牢固;修复组织的细胞为透明软骨样细胞,柱状排列,Ⅱ型胶原染色阳性,与周围软骨及软骨下骨整合良好,且实验组组织学评分优于对照组和空白对照组 (P < 0.01)。对照组缺损处修复组织呈纤维样,与周围软骨未结合,空白对照组缺损区无修复组织,两组均无Ⅱ型胶原染色阳性表达。表明同种异体脱钙骨基质与骨髓间充质干细胞共培养后植入膝关节可形成软骨样组织,有效修复关节软骨缺损。     

Protective effects of tumor necrosis factor-α blockade by adalimumab on articular cartilage and subchondral bone in a rat model of osteoarthritis

We aimed to investigate the effects of an anti-tumor necrosis factor-α antibody (ATNF) on cartilage and subchondral bone in a rat model of osteoarthritis. Twenty-four rats were randomly divided into three groups: sham-operated group (n=8); anterior cruciate ligament transection (ACLT)+normal saline (NS) group (n=8); and ACLT+ATNF group (n=8). The rats in the ACLT+ATNF group received subcutaneous injections of ATNF (20 μg/kg) for 12 weeks, while those in the ACLT+NS group received NS at the same dose for 12 weeks. All rats were euthanized at 12 weeks after surgery and specimens from the affected knees were harvested. Hematoxylin and eosin staining, Masson''s trichrome staining, and Mankin score assessment were carried out to evaluate the cartilage status and cartilage matrix degradation. Matrix metalloproteinase (MMP)-13 immunohistochemistry was performed to assess the cartilage molecular metabolism. Bone histomorphometry was used to observe the subchondral trabecular microstructure. Compared with the rats in the ACLT+NS group, histological and Mankin score analyses showed that ATNF treatment reduced the severity of the cartilage lesions and led to a lower Mankin score. Immunohistochemical and histomorphometric analyses revealed that ATNF treatment reduced the ACLT-induced destruction of the subchondral trabecular microstructure, and decreased MMP-13 expression. ATNF treatment may delay degradation of the extracellular matrix via a decrease in MMP-13 expression. ATNF treatment probably protects articular cartilage by improving the structure of the subchondral bone and reducing the degradation of the cartilage matrix.     

金骨莲灌胃对兔骨关节炎模型软骨细胞凋亡相关蛋白表达的影响

文题释义： 细胞凋亡：为维持内环境稳定，由基因控制的细胞自主有序的死亡。与细胞坏死不同，细胞凋亡不是一件被动的过程，而是主动过程，它涉及一系列基因的激活、表达以及调控等作用，是为更好地适应生存环境而主动争取的一种死亡过程。 P-p38蛋白：磷酸化p38蛋白，存在于P38MAPK信号通路中，该通路是丝裂原活化蛋白激酶的亚类之一，该通路中的特异性p38蛋白经过磷酸化级联反应直接磷酸化，从而被激活并具备生物活性，存在于软骨组织中，可反映骨关节炎严重程度。 背景：金骨莲胶囊为传统的苗药组方，其成分主要包含金铁锁、汉桃叶等成分，既往研究表明该药物具有软骨保护作用，但对其软骨保护的机制还不清楚。 目的：探讨金骨莲灌胃治疗骨关节炎的可能机制。 方法：从40只家兔中随机挑选10只作为空白对照组，余下的30只家兔以改良Hulth法在兔右侧后膝建立骨关节炎模型，并随机分为骨关节炎模型组(10只)、金骨莲灌胃组(10只)，p38抑制剂组(10只)。建模7 d后，金骨莲灌胃组给予金骨莲与双蒸水混合液10 mL灌胃[57.5 mg/(kg·d)]；p38抑制剂组给予兔右侧后膝关节腔注射10 μmol/L p38抑制剂(SB203580)0.5 mL，每周1次；空白对照组及骨关节炎模型组仅灌服等量双蒸水，1次/d，干预8周后处死动物取右侧后膝关节股骨髁及胫骨平台。采用Pelletier评分评估软骨损伤情况；苏木精-伊红染色、番红O染色及Mankin评分评估软骨退变情况；Western blot检测软骨组织中P-p38及Cleaved Caspase-3蛋白的表达；实时荧光定量PCR检测各组软骨组织中Bcl-2、Bax mRNA表达。 结果与结论：①金骨莲灌胃组Pelletier评分及Mankin评分较骨关节炎模型组及p38抑制剂组明显降低(P < 0.05)；②金骨莲灌胃组软骨组织中Bax mRNA、Cleaved Caspase-3蛋白表达较骨关节炎模型组及p38抑制剂组明显降低(P < 0.05)；③金骨莲灌胃组Bcl-2 mRNA的表达较骨关节炎模型组及p38抑制剂组均明显升高(P < 0.05)；④金骨莲灌胃组软骨组织中P-p38蛋白表达较骨关节炎模型组与p38抑制剂组明显降低(P < 0.05)；⑤结果表明，金骨莲可抑制骨关节炎模型兔软骨组织中凋亡相关蛋白和P-p38蛋白的表达，从而延缓关节软骨退变。 ORCID: 0000-0002-6664-8008(彭旭) 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程     

The electron microscope appearance of the subchondral bone plate in the human femoral head in osteoarthritis and osteoporosis

The subchondral bone plate supports the articular cartilage in diarthrodial joints. It has a significant mechanical function in transmitting loads from the cartilage into the underlying cancellous bone and has been implicated in the destruction of cartilage in osteoarthritis (OA) and its sparing in osteoporosis (OP), but little is known of its composition, structure or material properties. This study investigated the microscopic appearance and mineral composition of the subchondral bone plate in femoral heads from patients with OA or OP to determine how these correspond to changes in composition and stiffness found in other studies. Freeze-fractured full-depth samples of the subchondral bone plate from the femoral heads of patients with osteoarthritis, osteoporosis or a matched control group were examined using back scattered and secondary emission scanning electron microscopy. Other samples were embedded and polished and examined using back-scattered electron microscopy and electron probe microanalysis. The appearances of the samples from the normal and osteoporotic patients were very similar, with the subchondral bone plate overlayed by a layer of calcified cartilage. Osteoporotic samples presented a more uniform fracture surface and the relative thicknesses of the layers appeared to be different. In contrast, the OA bone plate appeared to be porous and have a much more textured surface. There were occasional sites of microtrabecular bone formation between the trabeculae of the underlying cancellous bone, which were not seen in the other groups, and more numerous osteoclast resorption pits. The calcified cartilage layer was almost absent and the bone plate was apparently thickened. The appearance of the osteoarthritic subchondral bone plate was, therefore, considerably different from both the normal and the osteoporotic, strongly indicative of abnormal cellular activity.     

丹参关节腔注射与针刺修复膝关节全层软骨缺损

背景：研究表明软骨下钻孔可有效修复关节软骨缺损,应用针药结合能有效控制软骨损伤出现的症状。推测针药结合可与软骨下钻孔在修复软骨缺损中产生协同作用。 目的：观察针药结合联合软骨下钻孔对兔膝关节全层软骨缺损的修复效果。 方法：于50只新西兰兔双侧股骨髁关节面造成6 mm×8 mm全层软骨缺损,随机分为5组。模型组造模后不作任何处理;钻孔组只做钻孔处理;丹参组钻孔后1周向膝关节腔注射丹参注射液0.3 mL,1次/周,共5周;针刺组钻孔后1周针刺兔双侧足三里穴,1次/d,30 min/次,6次为1个疗程,共治疗5个疗程;针药组钻孔后1周同时行丹参关节腔注射与针刺治疗,方法和疗程同上。 结果与结论：组织学及透射电镜检查均显示,模型组主要为纤维组织,其余4组缺损修复组织均为类透明软骨、幼稚软骨和纤维软骨,且以针药组修复组织的数量和质量最佳。与模型组比较,其余4组的致密修复组织覆盖缺损的面积明显增大(P < 0.01),以针药组的疗效最优,丹参组、针刺组次之。结果提示丹参关节腔注射、电针足三里和针药结合均可促进软骨下钻孔修复关节软骨缺损,且针药结合优于单纯的丹参关节腔注射及电针足三里治疗。     

TGFβ1-modified MSC-derived exosome attenuates osteoarthritis by inhibiting PDGF-BB secretion and H-type vessel activity in the subchondral bone

BackgroundGreater bone resorption increases TGF-β1 release and nestin-positive BMSC recruitment to the subchondral bone marrow, leading to excessive subchondral osteophyte formation and severe wear to articular cartilage. Our previous research demonstrated that BMSCs-Exo^TGF-β1 attenuated cartilage damage in osteoarthritis (OA) rats through carrying highly expressed miR-135b.MethodsThe bone marrow mesenchymal stem cells (BMSCs) were isolated from mouse bone marrow, and BMSC-derived exosomes (BMSCs-Exo) were isolated from BMSCs. OA mouse models were established by anterior cruciate ligament transection (ACLT) surgery on the left knee of mice. Then we explored the therapeutic effect of BMSCs-Exo^TGF-β1 on ACLT mice.ResultsBMSCs-Exo^TGF-β1 attenuated cartilage damage in OA mice in vivo by ameliorating articular cartilage degeneration and suppressing calcification of the cartilage zone. BMSCs-Exo^TGF-β1 also inhibited osteoclastogenesis by suppressing the MAPK pathway in vitro. Micro-computed tomography indicated that BMSCs-Exo^TGF-β1 impeded uncoupled subchondral bone remodeling. BMSCs-Exo^TGF-β1 also reduced CD31^hiEmcn^hi vessel activity in the subchondral bone and attenuated OA pain behaviors.ConclusionsIn conclusion, BMSCs-Exo^TGF-β1 maintains the microarchitecture, inhibits abnormal angiogenesis in subchondral bone and exerts protective effect against OA-induced pain and bone resorption on ACLT mice.Data availabilityThe datasets are available from the corresponding author on reasonable request.     

Micro-CT评价铁超载影响膝骨关节炎模型小鼠软骨类组织的变化

背景：膝骨关节炎可能与铁代谢异常有关,了解铁超载对膝骨关节炎的作用非常有意义。目的：探究铁超载对膝骨关节炎发病的影响。方法：选取30只7周龄C57B/6J野生型小鼠,采用随机数表法分为正常对照组、手术对照组与手术+右旋糖酐铁组,每组10只。8周龄时,手术+右旋糖酐铁组腹腔注射右旋糖酐铁500 mg/kg,每周1次,注射至18周龄时停止;10周龄时,手术对照组与手术+右旋糖酐铁组行左后膝内侧半月板失稳手术。18周龄时处死所有小鼠,通过Micro-CT检测胫骨微结构参数,番红O-固绿染色观察关节软骨组织病理损伤程度,普鲁士蓝染色证实铁在小鼠关节中的沉积。结果与结论：(1)Micro-CT检测显示,与正常对照组相比,手术对照组、手术+右旋糖酐铁组骨小梁相对体积、骨小梁厚度、骨小梁数量明显减小(P <0.05),骨小梁分离度、结构模型指数增加(P <0.05);与手术+右旋糖酐铁组比较,手术对照组骨小梁相对体积、骨小梁厚度、骨小梁数量增加(P <0.05),骨小梁分离度、结构模型指数相减小(P <0.05);(2)番红O染色显示,与正常对照组、手术对照组相比,手术+右旋...     

多孔丝素蛋白/羟基磷灰石复合脂肪间充质干细胞修复兔关节软骨及软骨下骨缺损

背景：丝素蛋白/羟基磷灰石是细胞立体培养的良好支架,是临床常用的骨缺损修复材料,具有良好的生物相容性。脂肪干细胞具有向骨及软骨细胞分化的潜能,适合骨软骨缺损修复。 目的：观察转化生长因子β1和胰岛素样生长因子1联合成软骨诱导脂肪干细胞与丝素蛋白/羟基磷灰石复合后修复兔关节软骨及软骨下骨缺损的效果。 方法：取新西兰大白兔56只,2只用于传代培养脂肪间充质干细胞,以3×109 L-1浓度接种到丝素蛋白/羟基磷灰石。其余54只新西兰大白兔,在股骨髁间制备软骨缺损模型,随机分为细胞复合材料组、单纯材料组和空白对照组,细胞复合材料组植入复合脂肪间充质干细胞的丝素蛋白/羟基磷灰石;单纯材料组植入丝素蛋白/羟基磷灰石;空白对照组不作任何植入。从大体、影像学、组织学观察比较缺损的修复情况。 结果与结论：12周时大体观察、CT、磁共振和组织学检查细胞材料复合组软骨及软骨下骨缺损区完全被软骨组织修复,修复组织与周围软骨色泽相近,支架材料基本吸收,未见明显退变和白细胞浸润,所有标本均未见丝素蛋白残留。单纯材料组缺损区缩小、部分修复,且呈纤维软骨样修复。空白对照组缺损无明显修复。提示复合脂肪间充质干细胞的丝素蛋白/羟基磷灰石修复兔关节软骨及软骨下骨缺损能力优于单纯丝素蛋白/羟基磷灰石材料。丝素蛋白/羟基磷灰石复合脂肪间充质干细胞可形成透明软骨修复动物膝关节全层软骨缺损,重建关节的解剖结构和功能,可作为新型骨软骨组织工程支架。