骨化三醇对大鼠骨性关节炎关节软骨及软骨下骨的影响

目的 观察骨化三醇对大鼠前交叉韧带切断术后膝关节软骨及软骨下骨的影响,探讨软骨下骨在骨性关节炎发病中的作用.方法 取SD大鼠64只分成4组,前交叉韧带切断组(ACLT组)、前交叉韧带切断+骨化三醇给药组(ACLT+cal组)、假手术组(sham组)、假手术+骨化三醇给药组(sham+cal组),给药组术后第2天给骨化三醇0.1 μg·kg-1·d-1灌胃,ACLT组和sham组给予安慰剂灌胃,持续2周.每组分别于术后2周和10周取材,胫骨近端切片后,行HE、AB-PAS染色、MMP-13免疫组化及骨形态计量学分析.结果 HE、AB-PAS染色、MMP-13免疫组化及骨形态计量学参数测量显示,2周时ACLT组与sham组相比早期有软骨下骨量减少,ACLT+cal组较ACLT组软骨下骨量增多(P<0.05).10周时ACLT组软骨明显退变性改变、软骨下骨增生及MMP-13表达增强,ACLT+cal组软骨退变及软骨下骨增生均较ACLT组减轻(P<0.01),MMP-13表达较ACLT组降低(P<0.05).结论 软骨下骨在骨性关节炎病变进展中发挥重要作用,骨代谢调节剂骨化三醇可减缓OA进展中软骨下骨硬化,对关节软骨有一定保护作用.     

降钙素对OA大鼠关节软骨及软骨下骨的保护作用

[目的]研究降钙素(calcitonin,CT)对骨性关节炎(OA)模型大鼠关节软骨和软骨下骨的保护作用.[方法]采用前叉韧带切断(anterior cruciate ligament transection,ACLT)法制备大鼠OA模型,30只12周龄雌性SD大鼠,随机分成3组:假手术组(Sham, n=10)、手术组(ACLT+NS, n=10)和给药组(ACLT+CT, n=10).术后ACLT+CT组皮下注射鲑鱼降钙素10 IU·kg-1·d-1,连续12周;ACLT+NS组则给予等量生理盐水.术后12周处死动物取材,采用Mankin评分系统评分;用双能骨密度仪测量右侧股骨远端1/4骨密度和股骨内外侧髁软骨下骨的骨密度;右侧股骨髁脱钙后切片,行番红"O"染色和MMP-13免疫组化染色;右侧胫骨近端做硬组织切片,测量软骨下松质骨的骨组织形态计量学参数.[结果](1)Sham组和ACLT+CT组关节软骨Mankin评分结果显著低于ACLT+NS组.(2)ACLT+NS组软骨下骨骨密度、骨量(BV/TV,Tb.Th)均显著高于Sham组及ACLT+CT组.(3)ACLT+NS组关节软骨MMP-13表达显著高于Sham组及ACLT+CT.[结论]降钙素10 IU·kg-1·d-1皮下注射12周能够抑制OA大鼠关节软骨的退变,其作用机制可能与下调关节软骨中MMP-13的表达及抑制软骨下骨的增生硬化并改善其微观结构有关.     

组蛋白去乙酰化酶4在大鼠骨关节炎软骨退变中的变化趋势及作用

目的 探讨组蛋白去乙酰化酶4（HDAC4）及其下游分子Runx-2在大鼠骨关节炎（osteoarthritis,OA）发生发展中的变化及对关节软骨退变的影响。方法 大鼠实验组肋软骨细胞添加10 ng/mL的IL-1β,对照组添加等体积的无菌PBS,48 h后行Western blot检测HDAC4和Runx-2的表达;构建ACLT大鼠OA模型,于术后2、4、8周通过番红固绿染色检测关节软骨退变情况,关节软骨损伤程度采用OARSI评分;同时,通过免疫组织化学染色和RT-qPCR检测HDAC4和Runx-2的表达量。结果 体外OA模型中,和对照组比,HDAC4的表达降低,Runx-2的表达升高（P＜0.05）;大鼠前交叉韧带切断组,番红固绿染色显示,大鼠术后时间的增加伴随着膝软骨破坏程度的增加,OARSI评分升高（P＜0.05）;免疫组化可见,术后的时间不断增加,HDAC4的表达逐渐降低,而Runx-2的表达逐渐升高（P＜0.05）。实时荧光定量PCR（RT-qPCR）显示,HDAC4 mRNA的表达随造模时间延长,其表达降低,而Runx-2 mRNA的表达逐渐升高（P＜0.05）。结论 在OA发生和进展过程中,HDAC4含量的不断降低,而其下游Runx-2的表达逐渐增加,可能和OA关节软骨退变相关。     

MMP-1、MMP-9 mRNA在创伤性骨关节炎软骨中的表达

目的 研究兔前交叉韧带横断术(ACLT)创伤性骨关节炎(OA)动态模型软骨中MMP-1、MMP-9 mRNA的表达,探讨MMP-1、MMP-9在OA软骨退变中的作用.方法 30只新西兰兔随机分为对照组(10只)、ACLT组(20只),ACLT组行右膝ACLT,对照组行关节囊切开缝合术,ACLT组于术后4、8 w各处死10只,对照组术后4 w处死.解剖显微镜观察股骨内髁软骨形态学变化,逆转录聚合酶链反应(RT-PCR)检测股骨内髁软骨MMP-1、MMP-9 mRNA的表达.结果 形态学示ACLT组软骨退变重于对照组(P<0.05),且ACLT 8 w组重于4 w组(P<0.05);RT-PCR示ACLT组MMP-1、MMP-9 mRNA表达量均高于对照组(P<0.01),且ACLT 8 w组均高于4 w组(P<0.01).结论 创伤性OA软骨退变过程中伴随着MMP-1、MMP-9 mRNA表达的上调,软骨中MMP-1、MMP-9 mRNA的表达一定程度上反映了OA软骨的退变程度.     

降钙素对兔骨关节炎关节软骨的保护作用

[目的]研究降钙素（ealcitonin，CT）对骨关节炎关节软骨的保护作用。[方法]6个月龄新西兰大白兔20只，随机分为两组均行右膝关节前交叉韧带切断术。1周后实验组开始皮下注射降钙素5 IU／kg，每日1次：对照组注入等剂量生理盐水；术后6周处死动物。取股骨内髁制成切片行HE、番红“O”和Ⅱ型胶原免疫组化染色。HE切片按照Mankin评分表评分。番红“O”染色和Ⅱ型胶原免疫组化染色切片用图像分析仪，测量平均灰度值。[结果]（1）对照组术侧膝关节组织学Mankin评分结果、番红“O”染色和Ⅱ型胶原免疫组化染色平均灰度值测量结果高于健侧，（P〈0．01）。（2）对照组手术膝关节组织学评分、番红“O”染色和Ⅱ型胶原免疫组化染色平均灰度值测量结果高于实验组手术膝关节，（P〈0．05）。[结论]降钙素5IU／kg每日1次皮下注射够明显减轻兔膝关节不稳定诱发的骨关节炎关节软骨的退变。降钙素可能通过提高软骨基质糖胺多糖（glycosaminoglycaris,GAG）和Ⅱ型胶原含量保护关节软骨。     

仙灵骨葆对兔膝骨性关节炎治疗作用的研究

[目的]研究仙灵骨葆(xianlinggubao, XLGB)对兔骨性关节炎关节软骨及软骨下骨的保护作用.[方法]30只3个月龄雄性日本大耳白兔,随机分为对照组(Sham)、盐水组(ACLT+NS)和仙灵骨葆组(ACLT+XLGB),每组各10只.盐水组和仙灵骨葆组行右膝关节前交叉韧带切断术(anterior cruciate ligament transaction, ACLT)造成膝骨性关节炎模型.术后仙灵骨葆组125 mg/(kg*d)灌胃;盐水组则给予等剂量生理盐水.6周后处死动物,取股骨测量骨密度,之后脱钙制片,行HE染色、Mankin评分及BMP-2、MMP-13免疫组化染色;取右膝胫骨近端包埋,制成硬组织切片,用于骨组织形态计量学测量.[结果](1)Mankin评分:仙灵骨葆组显著低于盐水组.(2)股骨远端骨密度及胫骨近端软骨下骨骨量:仙灵骨葆组均显著高于盐水组.(3)免疫组化:仙灵骨葆组MMP-13的表达显著低于盐水组,BMP-2的表达显著高于盐水组.[结论]仙灵骨葆125 mg/(kg*d)灌胃能够部分阻止骨关节炎兔关节软骨的退变,其作用机制可能与下调MMP-13的表达,上调BMP-2的表达,同时增加软骨下骨骨量,改善其微观结构有关.     

阿仑膦酸钠对前交叉韧带切断大鼠关节软骨退变的影响

[目的]观察阿仑膦酸钠(alendronate,ALN)对前交叉韧带切断术(anterior cruciate ligament transaction,ACLT)后骨关节炎模型大鼠膝关节软骨和软骨下骨的影响.[方法]24只3个月龄雌性SD大鼠按体重随机分为假手术组(Sham,n=8)、手术组(ACLT+NS,n=8)及给药组(ACLT+ALN,n=8),术后ALN组给予阿仑膦酸钠20 μg·kg-1·2 d-1皮下注射,连续给药12周;ACLT组则给予等剂量无菌生理盐水.股骨远端软骨下骨骨密度和胫骨近端骨组织形态计量学分析,通过关节软骨Mankin评分和MMP-13免疫组化染色观察关节软骨的退变和软骨基质的降解程度.[结果](1)ACLT+NS组股骨内侧髁骨密度显著低于Sham组和ACLT+ALN组(P＜0.05);(2)ACLT+ALN组的胫骨近端骨量显著高于ACLT+NS组(P＜0.05);(3)ACLT+ALN组的关节软骨Mankin评分和MMP-13免疫组化染色平均积分光密度显著低于ACLT+Ns组(P＜0.05).[结论]阿仑膦酸钠20 μg·kg-1·2 d-1皮下注射12周可以预防ACLT大鼠关节软骨退变,其作用机制可能与下调MMP-13的表达和增加软骨下骨骨量有关.     

独活挥发油灌胃对兔膝骨关节炎的保护作用及其机制

目的探讨独活挥发油(VOOA)灌胃对兔膝骨关节炎(OA)的保护作用及其机制。方法 6月龄日本大耳白兔24只,采用右膝关节前交叉韧带切断术(ACLT)建立兔膝OA模型,随机分为4组:模型组(OA组)、假手术组(Sham组)、盐水组(ACLT+NS组)和VOOA组(ACLT+VOOA组),每组6只。ACLT+VOOA组术后予以VOOA 0.2 ml/(kg.d)灌胃,ACLT+NS组给予等量的生理盐水。8周后处死动物,采用肉眼观察各组软骨及滑膜组织,病理切片行HE染色并进行软骨Mankin评分;检测血清及关节液内白细胞介素1(IL-1)、生长转化因子β(TGF-β)的含量;免疫组织化学法测定软骨中IL-1、TGF-β的含量。结果 ACLT+VOOA组可见软骨破坏减轻,滑膜纤维增生减少,Mankin评分低于ACLT+NS组及OA组,差异有统计学意义(P<0.05);血清、膝关节滑液IL-1含量低于ACLT+NS组及OA组,差异有统计学意义(P<0.05);TGF-β表达量高于ACLT+NS组、OA组及Sham组,差异有统计学意义(P<0.05)。结论 VOOA灌胃能够部分阻止兔OA关节软骨的退变,其机制可能为减少滑液中炎性介质IL-1的分泌、促进TGF-β的分泌,从而减轻滑膜炎症、缓解对软骨细胞的破坏。     

降钙素在体内体外实验中对兔关节炎关节软骨退变及软骨下骨骨代谢的影响

[目的]研究降钙素(calcitonin, CT)对骨性关节炎关节软骨退变和软骨下骨骨代谢的影响.[方法]30只3个月龄雌性日本大耳白兔随机分为三组,其中两组行右膝关节前交叉韧带切断术(anterior cruciate ligament transaction,ACLT),分为ACLT+CT组和ACLT+NS组,第3组为Sham组.ACLT+CT给予每日1次皮下注射降钙素5 IU/(kg·d),持续8周,ACLT+NS组给予同样剂量生理盐水.术后8周后处死所有动物.取股骨髁制成切片行MMP-13和Ⅱ型胶原免疫组化染色.取胫骨近端制成硬组织切片行骨形态计量学检测.体外实验中,取兔膝关节软骨,经消化、培养,将第3代软骨细胞分三组:向IL-1β组加入人重组IL-1β(10 ng/ml). IL-1β+CT组加入人重组IL-1β (10 ng/ml)2 d后,再向培养液中加入CT(50 ng/ml).正常组不加任何诱导剂和干扰剂培养.然后行MMP-13、Ⅱ型胶原免疫组化检测和Realtime RT-PCR法检测.[结果]Sham组和ACLT+CT组软骨下骨骨小梁相对体积和厚度等均显著高于ACLT+NS组.Sham组和ACLT+CT组的Ⅱ型胶原的光密度值均显著高于ACLT+NS组,而MMP-13的光密度值显著低于ACLT+NS组(P<0.05).正常组和IL-1β+CT组的Ⅱ型胶原光密度值均显著高于IL-1β组而MMP-13的光密度值都显著低于IL-1β组(P<0.05).在正常组和IL-1β+CT组中Ⅱ型胶原的mRNA含量均显著高于IL-1β组而MMP-13的mRNA含量均显著低于IL-1β组(P<0.05).[结论]降钙素5 IU/(kg·d)皮下注射能够增加ACLT兔膝关节软骨Ⅱ型胶原的分泌和抑制MMP-13的表达,并可能通过调节软骨下骨的骨代谢和微结构来保护关节软骨; CT(50 ng/ml)能增加体外培养的含有IL-1β(10 ng/ml)的软骨细胞中Ⅱ型胶原的含量和抑制MMP-13分泌.     

Characterization of articular cartilage and subchondral bone changes in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis

Osteoarthritis (OA) is a chronic joint disease characterized by cartilage destruction, subchondral bone sclerosis, and osteophyte formation. Subchondral bone stiffness has been proposed to initiate and/or contribute to cartilage deterioration in OA. The purpose of this study was to characterize subchondral bone remodeling, cartilage damage, and osteophytosis during the disease progression in two models of surgically induced OA. Rat knee joints were subjected either to anterior cruciate ligament transection (ACLT) alone or in combination with resection of medial menisci (ACLT + MMx). Histopathological changes in the surgical joints were compared with sham at 1, 2, 4, 6, and 10 weeks post-surgery. Using a modified Mankin scoring system, we demonstrate that articular cartilage damage occurs within 2 weeks post-surgery in both surgical models. Detectable cartilage surface damage and proteoglycan loss were observed as early as 1 week post-surgery. These were followed by the increases in vascular invasion into cartilage, in loss of chondrocyte number and in cell clustering. Histomorphometric analysis revealed subchondral bone loss in both models within 2 weeks post-surgery followed by significant increases in subchondral bone volume relative to sham up to 10 weeks post-surgery. Incidence of osteophyte formation was optimally observed in ACLT joints at 10 weeks and in ACLT + MMx joints at 6 weeks post-surgery. In summary, the two surgically induced rat OA models share many characteristics seen in human and other animal models of OA, including progressive articular cartilage degradation, subchondral bone sclerosis, and osteophyte formation. Moreover, increased subchondral bone resorption is associated with early development of cartilage lesions, which precedes significant cartilage thinning and subchondral bone sclerosis. Together, these findings support a role for bone remodeling in OA pathogenesis and suggest that these rat models are suitable for evaluating bone resorption inhibitors as potential disease-modifying pharmaco-therapies.     

Development and regulation of osteophyte formation during experimental osteoarthritis

OBJECTIVES: Osteophytes represent areas of new cartilage and bone formation in human and experimentally induced osteoarthritis (OA). The present study addressed the production of nitric oxide (NO), vascular endothelial growth factor (VEGF) and the occurrence of apoptosis during osteophyte formation. DESIGN: Osteophytes in the knee joint of rabbits that developed OA-like lesions following anterior cruciate ligament transection (ACLT) were analysed by histology and immunohistochemistry for NO production, and the presence of VEGF. TUNEL was used to detect DNA fragmentation. RESULTS: At the joint margins in the interface between cortical bone marrow and periosteal lining growth plate-like formations were detectable as early as 4 weeks after ACLT. By 12 weeks after ACLT osteophytes were visible in 100% of femoral condyles and tibial plateaus. Discrete areas with proliferating chondrocytes, hypertrophic chondrocytes, calcified matrix and vascular invasion were observed. VEGF immunoreactivity was most prominent in hypertrophic chondrocytes 9 weeks after ACLT. Nitrotyrosine immunoreactivity was detected in endothelial cells and in some hypertrophic chondrocytes in the calcified zone 4 weeks after ACLT. After 8 and 12 weeks, positive cells were detected in the hypertrophic and calcified zone. TUNEL-positive cells were seen in blood vessels, and among hypertrophic chondrocytes adjacent to the blood vessels 4 weeks after ACLT. The proliferative zone, pre-hypertrophic zone and hypertrophic zone showed only a few TUNEL positive cells. In contrast, 8 weeks and 12 weeks after ACLT, most hypertrophic chondrocytes, but few proliferative chondrocytes showed DNA fragmentation. CONCLUSIONS: Hypertrophic chondrocytes in osteophytes express VEGF and this can promote vascular invasion of cartilage. The presence of TUNEL-positive cells shows a similar distribution as nitrotyrosine immunoreactivity during all phases of osteophyte development, suggesting that NO production and chondrocyte death are related events in osteophyte formation.     

Association between subchondral bone structure and osteoarthritis histopathological grade

Despite increasing evidence that subchondral bone contributes to osteoarthritis (OA) pathogenesis, little is known about local changes in bone structure compared to cartilage degeneration. This study linked structural adaptation of subchondral bone with histological OA grade. Twenty‐five osteochondral samples of macroscopically different degeneration were prepared from tibiae of 14 patients. Samples were scanned with micro‐computed tomography (μCT) and both conventional structural parameters and novel 3D parameters based on local patterns were analyzed from the subchondral plate and trabecular bone. Subsequently, samples were processed for histology and evaluated for OARSI grade. Each bone parameter and OARSI grade was compared to assess structural adaptation of bone with OA severity. In addition, thicknesses of cartilage, calcified cartilage, and subchondral plate were analyzed from histological sections and compared with subchondral bone plate thickness from μCT. With increasing OARSI grade, the subchondral plate became thicker along with decreased specific bone surface, while there was no change in tissue mineral density. Histological analysis showed that subchondral plate thickness from μCT also includes calcified cartilage. Entropy of local patterns increased with OA severity, reflecting higher tissue heterogeneity. In the trabecular compartment, bone volume fraction and both trabecular thickness and number increased with OARSI grade while trabecular separation and structure model index decreased. Also, elevation of local patterns became longitudinal in the subchondral plate and axial transverse in trabecular bone with increasing OARSI grade. This study demonstrates the possibility of radiological assessment of OA severity by structural analysis of bone. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. J Orthop Res 35:785–792, 2017.

     

兔骨关节炎软骨细胞骨架变化的研究

目的探讨软骨细胞骨架的形态及含量变化在骨关节炎(OA)发病机制中的作用。方法 3月龄雄性新西兰白兔8只,随机分为2组,每组4只,实验组行前交叉韧带切断术(ACLT),造成OA模型,对照组切开关节囊,但不行ACLT。20周后处死两组动物,取左膝做大体标本观察,行Mankin's评分及HE染色。右膝在无菌条件下取全层软骨,消化分离软骨细胞,荧光染色后用激光共聚焦扫描显微镜对软骨细胞骨架进行形态学观察及荧光强度定量检测,对数据进行两独立样本t检验和非参数检验。结果手术后20周实验组关节软骨明显退变,Mankin's评分明显高于对照组(t=7.23,P0.05);和对照组相比,实验组波形蛋白、微管、纽蛋白形态及分布发生明显改变,荧光定量检测显示实验组中间纤维、微管和纽蛋白均低于对照组(t波形蛋白=5.40,t微管=11.86,t纽蛋白=5.21,P0.001),微丝形态和含量两组间无统计学差异。结论 OA软骨细胞骨架中间纤维、微管和纽蛋白发生明显改变,可能与OA的发病机制有一定关系。     

Osteochondral alterations in osteoarthritis

Osteoarthritis (OA) is a major cause of pain and disability in the aging population, but its pathogenesis remains incompletely understood. Alterations beneath the articular cartilage at the osteochondral junction are attracting interest as possible mediators of pain and structural progression in OA. Osteochondral changes occur early during the development of OA and may aggravate pathology elsewhere in the joint. Loss of osteochondral integrity removes the barrier between intra-articular and subchondral compartments, exposing subchondral bone and its nerves to abnormal chemical and biomechanical influence. Osteochondral plasticity results in a merging of tissue compartments across the junction. Loss of the clearly differentiated demarcation between bone and articular cartilage is associated with invasion of articular cartilage by blood vessels and sensory nerves, and advancing endochondral ossification. Increased subchondral bone turnover is intimately associated with these alterations at the osteochondral junction. Cells signal across the osteochondral junction, and this cross-talk may be both a consequence of, and contribute to these pathological changes. Bone turnover, angiogenesis and nerve growth are also features of other diseases such as osteoporosis and cancers, for which therapeutic interventions are already advanced in their development. Here we review pathological changes at the osteochondral junction and explore their potential therapeutic implications for OA. This article is part of a Special Issue entitled "Osteoarthritis".     

Similarities and discrepancies in subchondral bone structure in two differently induced canine models of osteoarthritis

In osteoarthritis (OA), cartilage degradation is accompanied by subchondral bone changes. The pathogenesis and physiology of bone changes in OA are still unclear. The changes in subchondral bone architecture and cartilage damage were compared in differently induced experimental models of OA. Experimental OA was induced bilaterally by anterior cruciate ligament transection (ACLT) or by cartilage trauma (Groove model); bilateral sham surgery served as control. Lysylpyridinoline (LP, bone resorption) and C‐telopeptide of type II collagen (CTX‐II, cartilage breakdown) were measured over time. At 20 weeks after surgery, the subchondral cortical plate and trabecular bone of the tibia were analyzed by micro–computed tomography (µCT) and cartilage degeneration was analyzed histologically and biochemically. In both models, cartilage degeneration and cortical subchondral plate thinning were present. CTX‐II levels were elevated over time in both models. Subchondral trabecular bone changes were observed only in the ACLT model, not in the Groove model. Correspondingly, LP levels were elevated over time in the ACLT model and not in the Groove model. Interestingly, the trabecular bone changes in the ACLT model were extended to the metaphyseal area. The early decrease in plate thickness, present in both models, as was cartilage damage, suggests that plate thinning is a phenomenon that is intrinsic to the process of OA independent of the cause/induction of OA. On the other hand, trabecular changes in subchondral and metaphyseal bone are not part of a common pathway of OA development and may be induced biomechanically in the destabilized and less loaded ACLT joint. © 2010 American Society for Bone and Mineral Research     

前交叉韧带切除后半月板变化及α2-巨球蛋白干预效果的初步研究

目的探讨兔骨关节炎(OA)模型膝关节前交叉韧带切除(ACLT)术后半月板的变化,及对关节腔内注射α2-巨球蛋白(α2M)对该变化的干预情况。方法健康的新西兰大白兔24只,按随机数字表分成5个时间点组,前2组各6只,后3组各4只,双侧膝关节自体对照。ACLT术后4、8、11和15周时,左侧膝关节注射用无菌生理盐水稀释成145mg/L的α2M为治疗侧,右侧膝关节注射等量无菌生理盐水为阴性对照侧,每次每侧0.4ml。术后4、8、11、15和21周行膝关节正侧位X光检查、半月板masson染色和电镜检查。结果ACLT模型建立成功,建模的时间越长,阴性对照侧的半月板病变越明显,ACLT后21周时,双侧膝未见明显关节间隙、骨赘及骨缺损等改变,而masson染色和电镜观察结果显示双侧关节半月板组织结构和细胞结构在4周时已发生较轻微的病理改变。与α2M治疗侧比较,阴性对照侧8～21周间半月板病变加重,21周后阴性对照侧的病变转变为不可逆的损伤;与阴性对照侧比较,α2M治疗侧的半月板退变速度稍慢,半月板纤维和细胞情况较好,但伴有滑膜的增生、侵袭。结论α2M可以减缓动物模型关节炎病变的进展速度,对滑膜增生的抑制作用较弱,α2M可能适合OA发病初期的保护性治疗和研究。     

Effects of calcitonin on subchondral trabecular bone changes and on osteoarthritic cartilage lesions after acute anterior cruciate ligament deficiency.

Because SBM may contribute to cartilage breakdown in OA, experimental OA was induced in dogs by transecting the anterior cruciate ligament of the knee and treating with either CT or a placebo. CT significantly reduced both SBM and cartilage lesions. This study supports the use of CT in the treatment of canine experimental OA. INTRODUCTION: Because subchondral bone remodeling (SBM) may contribute to cartilage breakdown in osteoarthritis (OA), we evaluated to what extend calcitonin (CT) might affect cartilage and bone changes in the early stages of canine experimental OA. MATERIALS AND METHODS: Twelve dogs underwent transection of the anterior cruciate ligament (ACLT) of the right knee. After ACLT, each animal received a daily nasal spray delivering either 400 U of CT (CT-treated group; n = 6) or a placebo (PL-treated group; n = 6). At day 84 after surgery, animals were killed, and cartilage changes were graded. BMD and volume fraction (BVF) were assessed by pQCT in different regions of interest (ROIs) of the subchondral cancellous bone of tibial plateaus (TPs).Statistics included a 2 x 2 factorial analysis with +/-CT as one factor and +/-ACLT as the other. RESULTS AND CONCLUSIONS: Nonoperated (N-OP) knees were normal in both groups. In the PL-treated group, ACLT knees all exhibited OA changes, which predominated in the medial knee compartment. Furthermore, compared with N-OP knees, the BMD and BVF of ACLT joints were both markedly reduced in medial TP but not in lateral TP. In contrast, in the CT-treated group, cartilage OA lesions of ACLT knees were significantly reduced, and there was no difference in BMD and BFV between N-OP and ACLT knees. These findings suggest that the loss of subchondral trabeculae contributes to cartilage breakdown, possibly by enhancing cartilage deformation on joint loading. By counteracting bone loss, CT reduced cartilage OA lesions, and thus, might be useful in the treatment of OA in cruciate-deficient dogs.     

Chondroprotective effect of alendronate in a rabbit model of osteoarthritis

The aim of this study was to determine how alendronate (ALN) alters cartilage degeneration and periarticular bone quality in a rabbit anterior cruciate ligament transection (ACLT) model of osteoarthritis (OA). Thirty rabbits underwent an ACLT on the left knee and a sham operation on the right knee. Fifteen rabbits received weekly subcutaneous injections of ALN (0.14 mg/kg) and 15 rabbits (the control [cont] group) received saline. Animal knees were divided into four groups: cont/sham, cont/ACLT, ALN/sham, and ALN/ACLT. Histological, radiological, and immunohistochemical indices were evaluated for each group. Bone volume ratios by micro‐computed tomography showed that ALN prevented periarticular bone loss. Histologically, the cont/ACLT group had significantly worse cartilage damage than the cont/sham group 12 weeks after the surgery. However, the ALN/ACLT group had mild cartilage degeneration compared with that of the ALN/sham group. Immunohistochemical analysis showed that ALN suppressed the expression of matrix metalloproteinase‐13, interleukin‐1β, type‐X collagen, vascular endothelial growth factor, and receptor activator of nuclear factor κB ligand in OA cartilage. ALN had a chondroprotective effect in an experimental rabbit model of OA. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29: 1572–1577, 2011     

在体阻断软骨下营养对关节软骨影响的实验研究

背景：关节软骨无血管分布,其营养来自关节液和软骨下骨,哪条营养通路对关节软骨更为重要是学者们争论的焦点。目的：研究软骨下营养对关节软骨的影响,并探讨软骨下营养与骨关节炎的关系。方法：45只5个月龄雄性新西兰大白兔,建立股骨滑车骨软骨缺损的动物模型,并随机分为3组：自体骨软骨块移植组（Control组,n=15）;假手术组（Sham组,n=15）,用环钻在股骨滑车钻取骨软骨块,将其置入管状PVC内,原位回植;阻断软骨下营养组（DNBM组,n=15）,取出骨软骨后,将其置入帽状PVC内,原位回植。术后4周、8周、12周,每组5只（10膝）,取出膝关节进行大体评分、组织学评分、软骨厚度测量、凋亡染色（TUNEL染色）。结果：与Control组相比,大体评分结果提示,DNBM组软骨无明显退变;组织学评分结果提示,术后12周时DNBM组软骨明显退变（P〈0.005）;软骨厚度测量结果提示,术后8周、12周时DNBM组软骨厚度明显变小（P=0.00）;TUNEL染色结果提示,术后8周、12周时DNBM组关节软骨细胞凋亡明显增加（P〈0.01）。结论：软骨下营养是软骨的重要营养来源,失去软骨下营养,软骨会逐渐发生退变。