Topographical variations in articular cartilage and subchondral bone of the normal rat knee are age-related

In osteoarthritis animal models the rat knee is one of the most frequently investigated joint. However, it is unknown whether topographical variations in articular cartilage and subchondral bone of the normal rat knee exist and how they are linked or influenced by growth and maturation. Detailed knowledge is needed in order to allow interpretation and facilitate comparability of published osteoarthritis studies. For the first time, the present study maps topographical variations in cartilage thickness, cartilage compressive properties and subchondral bone microarchitecture between the medial and lateral tibial compartment of normal growing rat knees (7 vs. 13 weeks). Thickness and compressive properties (aggregate modulus) of cartilage were determined and the subchondral bone was analyzed by micro-computed tomography. We found that articular cartilage thickness is initially homogenous in both compartments, but then differentiates during growth and maturation resulting in greater cartilage thickness in the medial compartment in the 13-week-old animals. Cartilage compressive properties did not vary between the two sites independently of age. In both age-groups, subchondral plate thickness as well as trabecular bone volume ratio and trabecular thickness were greater in the medial compartment. While a high porosity of subchondral bone plate with a high topographical variation (medial/lateral) could be observed in the 7-week-old animals, the porosity was reduced and was accompanied by a reversion in topographical variation when reaching maturity. Our findings highlight that there is a considerable topographical variation in articular cartilage and subchondral bone within the normal rat knee in relation to the developmental status.     

Degenerative knee joint lesions in mice after a single intra-articular collagenase injection. A new model of osteoarthritis.

A single intra-articular injection with bacterial collagenase in the right knee joints of 10-week-old male C57bl10 mice led to osteoarthritic lesions within a few weeks in these joints. The collagenase-induced osteoarthritis was characterized by severe degenerative cartilage lesions on the medial side of the femorotibial joint associated with patellar dislocation to the medial side of the joint, sclerosis of subchondral bone below the cartilage erosions, osteophyte formation, and consequent deformity of the knee joints. The osteoarthritic alterations in the collagenase model closely resembled the changes observed in spontaneous osteoarthritis in aged mice. The intra-articular injection with collagenase probably results in damage to collagen type I-containing joint structures, such as tendons, ligaments and menisci, leading to an instable knee joint that results in the osteoarthritic joint lesions observed in this model. The collagenase-induced osteoarthritis model offers the possibility of studying experimental osteoarthritis in large animal groups of inbred strains within a restricted time span at low costs.     

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。     

An experimental canine model for subchondral lesions of the knee joint

Aim of the study was to create an animal model for the investigation of the role of subchondral bone damage without initial cartilage lesion in the pathogenesis of osteoarthritis, the mechanical properties of the joints as well as its role in cartilage metabolism. Therefore, after cadaver studies an animal model was created to apply a transarticular load to the femoro-patellar joint under reproducible conditions and produce a pure subchondral damage without affecting the articular cartilage. Following the cadaver studies a first group of four dogs was impacted to identify forces to produce isolated subchondral fractures in the femoral condyle. Then a second group of 12 dogs knee joints was impacted under identical conditions with forces of approximately 2100 N to produce similar subchondral fractures without cartilage damage in one joint under MRI control: T1-weighted SE-sequences. T2-weighted TSE, fat suppressed TIRM-sequences and 3D-FLASH fat saturated sequences. FLASH 3D-sequences revealed intact cartilage after impact in all cases and TIRM-sequences showed subchondral fractures representing bleeding, microfractures and fragmented bone trabecules. Turbo spin echo sequences and T1-weighted images revealed other intact intraarticular structures such as ligaments and menisci. The proposed experimental animal model is suitable to investigate the effect of pure subchondral damage on the articular cartilage and on means of treatment of cartilage defects without surgical intervention and without initial cartilage damage.     

间充质干细胞治疗骨关节炎的临床研究进展

骨关节炎(OA)是一种进展性疾病,表现为软骨缺损、滑膜炎症、软骨下骨硬化及骨赘形成,关节表面软骨再生能力弱,无法实现自我修复.骨关节炎患者的主要临床表现为疼痛和关节活动受限,肢体功能和生活质量受影响.理想的治疗方案应缓解疼痛、促进软骨修复,以延缓或阻止病程进展.间充质干细胞(MSCs)在治疗骨关节炎方面具备以上优势且无...     

Involvement of the proximal tibiofibular joint in osteoarthritis of the knee

This study was performed to evaluate the possible involvement of the proximal tibiofibular joint in primary osteoarthritis of the knee. A total of 40 patients with primary osteoarthritis of the knee who had magnetic resonance imaging scans were reexamined for proximal tibiofibular joint involvement. The patient was questioned if pain was present in the proximal tibiofibular joint while at rest, when walking and climbing stairs. Symptoms were evaluated by applying moderate compression over the proximal tibiofibular joint during active ankle and knee motions. Magnetic resonance imaging scans were reexamined by two radiologists. Three of the 40 patients had minimal or moderate pain in the proximal tibiofibular joint during stair-climbing and on clinical examination. Magnetic resonance imaging scans of these three patients revealed osteophyte or subchondral cyst formation, or both. Degenerative changes in the proximal tibiofibular joint may be evident in association with osteoarthritis of the knee and may result in lateral-sided pain at the knee.     

软骨下骨病理骨重建过程中骨细胞的代谢机制

背景：骨性关节炎一直被认为是关节软骨的退变和降解。现已逐步认识到软骨下骨结构及分子代谢的病理变化在关节退变的过程中发挥了重要的作用。 目的：观察软骨下骨在骨性关节炎进程中结构及细胞、相关因子和信号通道的变化,分析软骨下骨的病理改变对关节软骨退变的影响。 方法：使用骨性关节炎、软骨下骨、软骨退变、骨重建、骨代谢等关键词,检索中国知识资源总库与PubMed、Medline、Embase数据库中的相关研究论文,了解骨性关节炎进程中软骨下骨骨代谢平衡破坏后在结构及分子信号机制的病理变化,分析这些病理改变与关节软骨退变的关系。 结果与结论：纳入 54篇符合标准的文献。软骨下骨的病理骨重建贯穿骨性关节炎的始终,局部骨细胞的代谢及干细胞分化异常与软骨退变相互影响。通过对软骨下骨病理骨重建过程中骨细胞代谢机制的深入了解,为骨性关节炎提供了新的治疗靶点。     

补肾健脾活血中药干预膝骨关节炎模型大鼠软骨细胞IL-1β/ERRα/SOX9/Col2α1信号通路的变化

文题释义：膝骨关节炎：是一种以膝关节软骨退变、破坏和骨质增生为主要特征的慢性关节病，多患于中老年人群，主要表现为膝关节疼痛，上下楼梯时疼痛加重，休息后缓解，局部肿胀，活动受限，晚期膝关节畸形，严重影响患者的生活质量。 雌激素：主要由卵巢分泌，分泌的雌激素进入血液循环发挥生物学效应，妇女绝经后卵巢功能衰退，雌激素分泌减少从而诱发膝骨关节炎。 背景：膝骨关节炎是最常见的退行性关节疾病，其发病率和致残率高，已严重影响患者的生活质量。研究发现，补肾健脾活血中药能够改善膝骨关节炎临床症状，但其具体机制仍未阐明。 目的：通过膝骨关节炎去势大鼠模型研究补肾健脾活血中药调节IL-1β/ERRα/SOX9/Col2α1信号通路治疗大鼠膝骨关节炎的作用机制。方法：6月龄SD雌性大鼠，随机分为空白对照组、模型组、实验组和阳性对照组，模型组、实验组和阳性对照组摘除卵巢及切除交叉韧带和内侧半月板制作去势大鼠膝骨关节炎模型，术后2周实验组采用补肾健脾活血中药灌胃，阳性对照组采用塞来昔布胶囊灌胃，空白对照组和模型组以生理盐水灌胃。连续灌胃6周后取血清及膝关节软骨组织，采用ELISA检测血清雌二醇含量，分别采用荧光定量PCR和Western blot检测关节软骨组织中IL-1β/ERRα/SOX9/Col2α1信号通路表达水平。结果与结论：与空白对照组比较，模型组白细胞介素1β表达量明显升高，雌二醇、雌激素受体相关受体α、SRY相关蛋白9、Ⅱ型胶原的α1链表达量明显降低(P < 0.05)；与模型组比较，实验组白细胞介素1β表达量明显降低(P < 0.05)，雌二醇、雌激素受体相关受体α、SRY相关蛋白9、Ⅱ型胶原的α1链表达量明显升高(P < 0.05)；与阳性对照组比较，实验组白细胞介素1β、雌激素受体相关受体α及Ⅱ型胶原的α1链表达量明显升高(P < 0.05)，SRY相关蛋白9表达量明显降低(P < 0.05)。实验结果表明，IL-1β/ERRα/SOX9/Col2α1信号通路参与膝骨关节炎软骨病变，补肾健脾活血中药可通过该机制发挥治疗作用。 ORCID: 0000-0002-5449-3942(霍少川) 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     

Post-traumatic Osteoarthritis in Rabbits Following Traumatic Injury and Surgical Reconstruction of the Knee

Post-traumatic osteoarthritis (PTOA) of the knee is often attributed to anterior cruciate ligament (ACL) and meniscus injury. The development of PTOA, however, does not seem to depend on whether or not the damaged ACL is reconstructed. There has been a need to develop animal models to study the mechanisms of PTOA following reconstruction of a traumatized knee. Eighteen rabbits underwent closed-joint trauma to produce ACL rupture and meniscus damage. Then, for the first time, the traumatized knee was surgically repaired in this animal model. Upon euthanasia at 1-, 3- or 6-month post-trauma, joint stability, cartilage morphology and mechanical properties, as well as histology of the cartilage and subchondral bone were evaluated. Trauma-induced knee injury involved 72% mid-substance ACL rupture, 28% partial ACL tear and 56% concurrent medial meniscal damage. ACL reconstruction effectively restored joint stability by reducing joint laxity to a level similar to that in the contralateral intact knee. Compared to their contralateral controls, reconstructed limbs showed osteoarthritic changes to the cartilage and subchondral bone as early as 1-month post-trauma. The degeneration progressed over time up to 6-month. Overall, the medial compartments had more tissue damage than their corresponding lateral counterparts. Damage patterns to the ACL, the frequency of observed concurrent meniscal injury, and reductions in cartilage integrity and health were consistent with clinical observations of human patients who undergo ACL injury and reconstruction. Thus, we believe the combined closed-joint injury and surgical repair lapine model of PTOA, being first-ever and clinically relevant, shows promise to evaluate well-targeted therapeutics and other interventions for this chronic disease.

     

骨关节炎软骨下骨中视网膜母细胞瘤RB1-诱导卷曲蛋白1的表达及作用

文题释义：视网膜母细胞瘤RB1-诱导卷曲蛋白1(RB1-inducible coiled-coil 1,RB1CC1)：是一种相对分子质量为200的FAK家族相互作用蛋白,最初通过酵母双杂交筛选鉴定为Pyk2相互作用蛋白,并可作为RB1基因的潜在调节因子,参与肿瘤细胞的周期调控。RB1CC1多在心脏、睾丸、肌肉骨骼以及小鼠胚胎等组织中大量表达,对细胞的生长、分化、凋亡和自噬起到重要的调控作用。 骨涎蛋白：是一种由成骨细胞、破骨细胞合成的磷酸化糖蛋白,相对分子质量为75,含有约300个氨基酸。在骨组织中大量表达,可特异性定位于矿化的骨组织内,参与成骨细胞和破骨细胞的骨代谢活动,是成骨细胞矿化成熟的标志。骨涎蛋白的RGD序列基因可与血管内皮细胞的整合素结合,从而引导软骨组织内血管形成。 背景：骨关节炎以关节软骨的退变和软骨下骨的重建为主要病理特征。骨关节炎的具体发病机制目前仍未清楚,大部分研究以软骨与软骨下骨为主要切入点,探索疾病过程中的分子机制和信号通路变化,为骨关节炎的诊断与治疗提供新的生物靶点和研究方向。 目的：探讨在骨关节炎进程中软骨下骨RB1CC1的表达情况。 方法：8周龄C57小鼠随机分为实验组和假手术组,实验组又随机分为4周和8周2个亚组。实验组小鼠行右侧膝关节内侧半月板胫骨韧带切除,游离内侧半月板,诱导骨关节炎;假手术组小鼠则仅切开关节囊而不行内侧韧带切除和半月板游离。实验方案于2017-12-13经南方医科大学第三附属医院动物实验伦理委员会批准,批准号为No.44007200038731。 结果与结论：与假手术组相比,实验组骨关节炎RSI评分均显著升高,关节软骨面Ⅱ型胶原表达降低,软骨下骨中的RB1CC1表达逐渐升高,RB1CC1与成骨相关指标BSP2的表达趋势有一致性;提示随着骨关节炎进程的发展,软骨下骨的RB1CC1表达逐渐增多,可能与促进软骨下骨增生及重塑有关。 ORCID: 0000-0002-2838-3707(蔡道章) 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     

兔实验性骨性关节炎早期软骨下骨板的变化

目的 观察兔膝骨性关节炎软骨下骨板与关节软骨之间联系,同时探讨应用降钙素手段干预软骨下骨板对骨性关节炎中关节软骨保护作用.方法 雄性日本大耳白兔随机分为3组,每组8只.对照组动物暴露右膝关节前交叉韧带而不予切断;模型组与实验组行右膝关节前交叉韧带切断术,术后实验组给予5 IU/(kg·d)降钙素皮下注射,模型组给予等量生理盐水,于术后8周处死所有动物并取材.关节软骨采用HE染色及Mankin评分、Von Gieson染色和基质金属蛋白酶-13免疫组织化学检测,软骨下骨板采用Von Kossa染色方法 进行组织形态计量学分析.结果 软骨组织形态学HE及Von Gieson染色显示,模型组关节软骨明显损伤,Mankin评分结果 显示,模型组评分显著高于对照组和实验组(P<0.05),实验组评分显著高于对照组(P<0.05);免疫组织化学染色及半定量分析表明,模型组基质金属蛋白酶-13表达显著高于对照组和实验组(P<0.05);模型组软骨下骨板形态被破坏,与对照组和实验组比较差异显著(P<0.05).结论 前交叉韧带切断诱导的骨性关节炎兔膝关节软骨与软骨下骨板组织结构同时被破坏,软骨下骨板与关节软骨间存在紧密关系,降钙素早期干预软骨下骨板,能够保护软骨下骨板组织形态结构,对关节软骨起到部分保护作用,延缓骨性关节炎病理进程.     

关节镜微创治疗膝关节骨性关节炎的疗效观察

目的探讨关节镜下微创治疗膝关节骨性关节炎（OA）的疗效。方法对129例膝关节OA患者行关节镜检及有限化微创清理术,采用HSS膝关节评定系统及Denis疼痛测定法进行术后疗效评定。结果术后随访6～36个月,129例中104例患者临床症状明显缓解,关节功能改善,优良率达80.62%。结论关节镜有限微创清理术能有效缓解OA症状,改善关节功能,提高生活质量。     

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。     

Effects of Risedronate on Osteoarthritis of the Knee

The purpose of the present study was to discuss the effects of risedronate on osteoarthritis (OA) of the knee by reviewing the existing literature. The literature was searched with PubMed, with respect to prospective, double-blind, randomized placebo-controlled trials (RCTs), using the following search terms: risedronate, knee, and osteoarthritis. Two RCTs met the criteria. A RCT (n = 231) showed that risedronate treatment (15 mg/day) for 1 year improved symptoms. A larger RCT (n = 1,896) showed that risedronate treatment (5 mg/day, 15 mg/day, 35 mg/week, and 50 mg/week) for 2 years did not improve signs or symptoms, nor did it alter radiological progression. However, a subanalysis study (n = 477) revealed that patients with marked cartilage loss preserved the structural integrity of subchondral bone by risedronate treatment (15 mg/day and 50 mg/week). Another subanalysis study (n = 1,885) revealed that C-terminal crosslinking telopeptide of type II collagen (CTX-II) decreased with risedronate treatment in a dose-dependent manner, and levels reached after 6 months were associated with radiological progression at 2 years. The results of these RCTs show that risedronate reduces the marker of cartilage degradation (CTX-II), which could contribute to attenuation of radiological progression of OA by preserving the structural integrity of subchondral bone. The review of the literature suggests that higher doses of risedronate (15 mg/day) strongly reduces the marker of cartilage degradation (CTX-II), which could contribute to attenuation of radiological progression of OA by preserving the structural integrity of subchondral bone.     

The influence of mechanical properties of subchondral plate, femoral head and neck on dynamic stress distribution of the articular cartilage

A few finite element models have addressed the dynamic juxtaarticular stress transmission but none focused the investigation on the combined influence of the individual moduli of the underlying bones, including the subchondral plate, the femoral head and the femoral neck of the proximal femur. A finite element model including the acetabulum and the proximal femur was analyzed with dynamic loadings to study the effects of mechanical property changes in the underlying bones of the proximal femur on the stress distribution in the cartilage at the hip joint. We found the stress distribution was most sensitive to the subchondral plate stiffening, while the overall stiffening of the underlying bones had mild effect on the shear stress on the cartilage surface (or at the subchondral bone/cartilage interface) and on the strain energy density in the cartilage. Our results indicate that the subchondral plate plays a predominant mechanical role in the initial degeneration of the cartilage. The results may offer a mechanical explanation as to why the cartilage failure is common in patients with osteoarthritis but rare in patients with osteoporosis.     

膝骨性关节炎患者胫骨软骨下骨超微结构改变的CT评价

文题释义： 膝骨性关节炎：是一种以渐进性的关节损伤为主要特征,并最终导致患者关节疼痛甚至残疾,极大地降低患者生活质量。 CT：利用精确准直的X射线束、γ射线、超声波等,与灵敏度极高的探测器一同围绕人体的某一部位作一个接一个的断面扫描,具有扫描时间快、图像清晰等特点。 背景：软骨下骨的改变在膝骨性关节炎的作用得到了越来越多的重视,但是既往研究主要以动物为观察对象,由于动物与人存在差异,因而直接在人体关节内获得相关数据是非常必要的。 目的：通过CT技术评价非膝骨性关节炎患者与膝骨性关节炎患者软骨下骨板及软骨下骨超微结构的区别,来探讨软骨下骨在膝骨性关节炎疾病的发生和发展中的作用。 方法：于2016年7月至2018年7月在郑州市骨科医院影像科就诊患者中,收集30例膝骨性关节炎患者(膝骨性关节炎组)及30例非膝骨性关节炎患者(非膝骨性关节炎组)的CT扫描数据,使用MIMICS软件比较2组胫骨平台内外侧软骨下骨板以及软骨下骨小梁超微结构。试验于2016-06-10经郑州市骨科医院伦理委员会审批通过,审批号为2016医院伦审第004号。 结果与结论：①与非膝骨性关节炎组相比,膝骨性关节炎组软骨下骨板在外侧部位和内侧部位骨密度都明显增加,孔隙率则出现显著的下降,而软骨下骨板厚度内侧部分较非膝骨性关节炎组显著增厚;②膝骨性关节炎软骨下骨小梁同样存在明显变化,表现为膝骨性关节炎组内外侧软骨下骨骨小梁厚度较非膝骨性关节炎组均明显增加,同时内侧松质骨分离度也较非膝骨性关节炎组低;膝骨性关节炎组结构模型指数和连接密度值低于非膝骨性关节炎组;③结果表明,膝骨性关节炎患者胫骨软骨下骨板及软骨下骨松质骨的改变主要在于超微结构稳态的破坏,这一改变可能是膝骨性关节炎发病原因之一。 ORCID: 0000-0002-9805-3084(白玉) 中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程     

膝关节股骨远端软骨硬化前后力学性能分析

目的建立膝关节有限元模型,研究正常及软骨硬化情况下膝关节的应力、应变变化,为临床治疗膝关节骨性关节炎提供参考。方法通过Mimics、ANSYS等软件结合正常膝关节CT扫描图像数据,建立膝关节三维有限元模型,并施加350 N压力载荷,设定软骨硬化前后相关的材料参数,分析膝关节主要组织的应力、应变改变情况。结果膝关节股骨远端软骨硬化后,关节软骨的减震和传递负荷等作用基本消失;股骨应力、应变变化量最大,受力分布极不均匀,股骨前端应力、应变较内、外侧髁明显,整体受力也有明显增加;半月板的应力、应变值最大。结论长期的软骨破坏会影响关节软骨营养代谢,导致骨性关节炎疾病进一步恶化。研究结果可以较好阐释骨性关节炎发病过程和机理,同时为建立参数化研究系统提供相关数据。     

电针治疗膝骨性关节炎患者上下楼梯的三维有限元分析

针对电针治疗膝骨性关节炎患者上下楼梯运动生物力学特性改变进行有限元仿真研究,对比分析膝关节生物力学行为改变与电针治疗疗效的相关性.基于CT和MRI图像数据,结合Mimics和Geomagic医学图像处理软件,建立人体膝关节下楼梯屈曲15°和上楼梯屈曲50°时的三维有限元模型,模型包括股骨、胫骨、腓骨、内外侧半月板、股骨...