基质金属蛋白酶9及TGF-β1 mRNA和蛋白在骨关节炎中的表达

目的 TGF-β1对骨关节炎(osteoarthritis,OA)关节软骨起保护作用,探讨OA中基质金属蛋白酶9(matrix metalloproteinase 9,MMP-9)、TGF-β1 mRNA和蛋白表达的相关性,为临床治疗OA寻找有效的干预靶点提供理论依据。方法取自愿捐赠的关节软骨及滑膜标本,其中OA患者60例(实验组),外伤截肢、交叉韧带断裂、盘状软骨损伤与半月板损伤患者20例(正常对照组)。行HE染色观察关节软骨与滑膜的病理组织学改变,免疫组织化学染色观测MMP-9及TGF-β1蛋白表达,原位杂交技术检测MMP-9及TGF-β1 mRNA表达;并进行相关性分析。结果 HE染色显示实验组关节软骨细胞固缩、坏死、排列紊乱,细胞外基质断裂,关节滑膜细胞肥大增生、淋巴细胞和单核细胞浸润,多数小血管增生;正常对照组软骨细胞排列整齐、基质染色均匀,滑膜组织无慢性炎症表现、无明显增生。两组均可见MMP-9、TGF-β1 mRNA和蛋白阳性表达,阳性细胞包括软骨细胞、滑膜衬里层细胞及滑膜下层的血管内皮细胞、成纤维细胞、炎性浸润细胞等。实验组MMP-9及TGF-β1 mRNA和蛋白表达均高于正常对照组(P<0.01)。实验组MMP-9 mRNA与蛋白表达成正相关(r=0.924,P=0.000),TGF-β1 mRNA及蛋白表达亦成正相关(r=0.941,P=0.000);实验组MMP-9及TGF-β1蛋白表达成负相关(r=—0.762,P=0.000),MMP-9 mRNA及TGF-β1 mRNA表达成负相关(r=?0.681,P=0.000)。结论 OA中TGF-β1的高表达下调了关节软骨与滑膜中MMP-9的表达,对OA关节软骨起保护作用,从而延缓OA进展。     

基质金属蛋白酶9及TGF-β_1 mRNA和蛋白在骨关节炎中的表达

目的 TGF-β1对骨关节炎(osteoarthritis,OA)关节软骨起保护作用,探讨OA中基质金属蛋白酶9(matrix metalloproteinase 9,MMP-9)、TGF-β1 mRNA和蛋白表达的相关性,为临床治疗OA寻找有效的干预靶点提供理论依据。方法取自愿捐赠的关节软骨及滑膜标本,其中OA患者60例(实验组),外伤截肢、交叉韧带断裂、盘状软骨损伤与半月板损伤患者20例(正常对照组)。行HE染色观察关节软骨与滑膜的病理组织学改变,免疫组织化学染色观测MMP-9及TGF-β1蛋白表达,原位杂交技术检测MMP-9及TGF-β1 mRNA表达;并进行相关性分析。结果 HE染色显示实验组关节软骨细胞固缩、坏死、排列紊乱,细胞外基质断裂,关节滑膜细胞肥大增生、淋巴细胞和单核细胞浸润,多数小血管增生;正常对照组软骨细胞排列整齐、基质染色均匀,滑膜组织无慢性炎症表现、无明显增生。两组均可见MMP-9、TGF-β1 mRNA和蛋白阳性表达,阳性细胞包括软骨细胞、滑膜衬里层细胞及滑膜下层的血管内皮细胞、成纤维细胞、炎性浸润细胞等。实验组MMP-9及TGF-β1 mRNA和蛋白表达均高于正常对照组(P<0....     

兔骨关节炎中基质金属蛋白酶-1、3与白细胞介素-1β表达及关节软骨细胞凋亡的研究

目的 观察骨关节炎(OA)中基质金属蛋白酶(MMP)-1、3与白细胞介素-1β(IL-1β)的表达及关节软骨细胞凋亡,探讨其在OA发病机制中的作用.方法 将20只中国大白兔随机分成正常组(A组)、实验组(B组),每组10只,A组未造模,B组采用Hulth法制成OA模型,4周后取胫骨平台关节软骨进行组织病理学检查,采用免疫组织化学和原位末端标记细胞凋亡检测法分别检测关节软骨和滑膜中的MMP-1、3、IL-1β及软骨细胞凋亡指数(AI)的水平.结果 组织病理学检查可见,B组关节软骨退变程度明显重于A组,符合OA关节软骨退变特征;通过检测MMP-1、3,IL-1β和AI,A组的结果分别是21.005±9.406、18.697±8.225、0.100±0.040和14.900±3.400,B组的结果分别是56.147±22.340、46.182±20.561、0.180±0.060和25.400 ±5.200;B组MMP-1、3和AI的水平均明显高于A组(P＜0.01),B组IL-1β水平高于A组(P＜0.05).结论 MMP-1、MMP-3、IL-1β的表达及关节软骨细胞凋亡在OA发病机制中作用重要,其异常升高与OA关节软骨退变和炎症反应密切相关.     

硫酸镁与氯化钠溶液灌洗对创伤性关节炎软骨损伤修复的影响

目的通过股骨髁间钻孔构建兔创伤性关节炎(PTOA)模型,比较相同渗透压下(400 mOsm/L)硫酸镁与氯化钠溶液持续灌洗对PTOA软骨损伤修复的影响。方法对18只新西兰白兔采用股骨髁间钻孔构建PTOA模型,随机分为PTOA组、氯化钠组和硫酸镁组,每组6只。ELISA检测关节腔积液白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、Ⅱ型胶原蛋白(CollagenⅡ)的表达,qPCR检测滑膜组织IL-1β、TNF-α、金属蛋白酶-3(MMP-3)基因表达。行软骨切片染色组织学观察及骨关节炎(OA)评分。结果关节腔积液IL-1β、TNF-α、CollagenⅡ分泌硫酸镁组少于PTOA组和氯化钠组,滑膜组织IL-1β、TNF-α和MMP-3 mRNA水平硫酸镁组低于PTOA组和氯化钠组;软骨组织切片OA评分硫酸镁组低于PTOA组和氯化钠组,差异均有统计学意义(P<0.05)。结论与相同渗透压下氯化钠溶液相比,硫酸镁溶液有利于减轻关节内炎症,减少CollagenⅡ及蛋白聚糖丢失,对软骨退变起到保护作用,有利于延缓PTOA病情进展。     

跳骨片抑制大鼠膝骨关节炎Wnt/β-catenin信号转导通路介导炎症反应的机制研究

目的探讨跳骨片对大鼠膝骨关节炎(OA)Wnt/β-catenin信号转导通路介导炎症反应的机制。方法将30只8周龄雄性SD大鼠随机分为空白组、模型组、跳骨片组,每组10只。空白组不予任何处理,模型组、跳骨片组均采用改良Hulth法建立OA动物模型。建模成功后跳骨片组每天予跳骨片0.32 g/kg灌胃,空白组和模型组每天予等量生理盐水灌胃,干预12周后分别取3组大鼠双侧膝关节股骨髁、关节软骨和滑膜,将股骨髁常规固定、脱钙、包埋及切片,对切片分别进行苏木精-伊红(HE)、甲苯胺蓝染色,光镜下观察关节软骨组织形态学变化;酶联免疫吸附测定(ELISA)检测滑膜中白细胞介素(IL)-1β、基质金属蛋白酶(MMP)-13、肿瘤坏死因子(TNF)-α含量;蛋白质免疫印迹检测关节软骨β-catenin、Wnt-4蛋白表达。结果模型组滑膜中,IL-1β表达量明显高于空白组和跳骨片组(P0.01),MMP-13表达量高于空白组和跳骨片组(P0.05),TNF-α表达量明显高于空白组(P0.01)、高于跳骨片组(P0.05);模型组关节软骨中,β-catenin蛋白表达量明显高于空白组和跳骨片组(P0.01),Wnt-4蛋白表达量高于空白组和跳骨片组(P0.05)。HE染色显示跳骨片组软骨破坏程度低于模型组,甲苯胺蓝染色显示跳骨片组软骨细胞蛋白多糖含量高于模型组(P0.01)。结论跳骨片能抑制关节软骨Wnt/β-catenin信号转导通路,降低滑膜中IL-1β、MMP-13、TNF-α表达,抑制炎症反应介导的软骨基质降解,延缓关节软骨退变。     

治疗型关节炎护膝干预膝骨性关节炎患者滑液细胞因子的研究

目的探讨治疗型关节炎护膝(OA护膝)干预膝骨性关节炎的作用机制。方法选择膝骨性关节炎患者60例,随机分为OA护膝组和微波组各30例,分别采用OA护膝和微波治疗。分别测定两组关节滑液白介素-1β(IL-1β)、白介素-6(IL-6)、肿瘤坏死因子-α(INF-α)、基质金属蛋白酶-3(MMP-3)、透明质酸(HA)浓度。结果护膝组X线Ⅰ、Ⅱ、Ⅲ级患者治疗后IL-1β、IL-6、INF-α、MMP-3含量比治疗前降低,而HA含量升高,结果比较差异有显著统计学意义(P0.01)。OA护膝组与微波组治疗后X线Ⅰ、Ⅱ级患者膝关节滑液IL-1β、IL-6、TNF-a、MMP-3、HA含量比较差异有统计学意义(P0.01,P0.05);两组X线Ⅲ级患者治疗后膝关节滑液IL-1β含量比较也差异有统计学意义(P0.05),而IL-6、INF-α、MMP-3、HA含量比较差异无统计学意义(P0.05)。结论 OA护膝可以有效调节细胞因子、MMP-3、HA的生物效应,从而延缓关节软骨的退变。     

NPWT促进糖尿病足溃疡创面愈合分子机制的初步研究

目的通过检测与创面愈合进程相关的组织基因表达,探讨采用负压创面治疗(nagetive pressure wound therapy,NPWT),促进糖尿病足溃疡(diabetic foot ulcer, DFU)愈合的作用机制。方法将纳入的50例DFU患者随机分成NPWT组(25例)和对照组(25例)。对照组接受局部湿敷治疗。两组患者治疗前后10 d均取创面肉芽行组织活检,利用RT-PCR检测转移生长因子-β1(transforminggrowth factor beta 1, TGF-β1)、血管内皮生长因子(vascular endothelial growth factor, VEGF)、肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)、白介素-1β(interleukin-1β, IL-1β)、基质金属蛋白酶-1(matrix metalloproteinase-1, MMP-1)、基质金属蛋白酶-9(matrixmetalloproteinase-9, MMP-9)和基质金属蛋白酶抑制剂-1(tissue inhibitor of metalloproteinase-1, TIMP-1)的mRNA表达,并进行对比分析。结果治疗后10 d,NPWT组患者创面肉芽组织中VEGF、TGF-β1和TIMP-1 mRNA的表达较治疗前显著增加,IL-1β、TNF-α、MMP-1和MMP-9 mRNA的表达显著下降(P<0.05);而对照组上述各项指标的mRNA表达,治疗前后均无显著变化(P>0.05)。结论 NPWT可能通过影响生长因子、炎症细胞因子和基质金属蛋白酶的表达来促进DFU愈合。     

MMP-12在类风湿关节炎中和骨性关节炎中的研究

目的基质金属蛋白酶(matrix metalloproteinase，MMPs)是分解细胞外基质的重要因子。人类金属弹性蛋白酶(human metallolastase，MMP-12)是MMPs的一种。现已证实由巨噬细胞分泌MMP-12的异常表达与许多疾病有关，如类风湿性关节炎(rheumatoid arthritis，RA)、骨性关节炎(osteoarthritis，OA)等。试验的目的是研究RA和OA病变中MMP-12在滑膜组织中的表达。方法滑膜组织取自临床确诊的22例RA及29例OA患者(均为膝或髋关节置换手术患者)，用免疫组织化学方法进行分析。结果免疫组化染色显示，表达MMP-12的细胞主要为滑膜层细胞．且大部分为炎性巨噬细胞。结论来源于巨噬细胞的MMY-12在RA病变发展，如关节破坏过程中起重要作用，抑制MMP-12高活性可能会为治疗RA提供一种新的途径。     

骨性关节炎与细胞因子相关性研究进展

骨性关节炎(osteoarthritis,OA)又称退行性关节炎,是由于关节组织发生了一系列生化变化,导致其组织正常降解与生成紊乱.近年来的研究表明,这些变化归因于一个复杂的细胞因子网络.当关节内存在炎性损伤时,会引起滑膜炎,继而刺激滑膜和软骨细胞产生细胞因子,如白介素-1(IL-1),肿瘤坏死因子-α(TNF-α),一氧化氮(NO),这些细胞因子会促使基质金属蛋白酶(matrix metalloproteinases,MMPs)和纤维蛋白溶酶原激活物(PA)增多,从而作用在关节软骨上,使之被破坏,继发性地引起胶原合成增多、软骨细胞增殖以及前列腺素(PG)合成增多.     

Changes in articular cartilage and subchondral bone histomorphometry in osteoarthritic knee joints in humans

In this study, we have examined the correlation between the histological and histochemical changes of articular cartilage and bone parameters of the underlying subchondral bone. The aim was to elucidate patterns of bone parameter changes within different depths of subchondral bone in the joints with macroscopically normal cartilage and in joints with osteoarthritis (OA). Ten tibial plateaus were taken from patients during total knee replacement surgery due to severe OA. They were compared with 10 sets of tibial condyles obtained from autopsy subjects with no history of bone or joint disease. The cylindrical cartilage-bone samples were taken out from the anterior, posterior, external, and internal areas of the condyles for cartilage assessment (Mankin score) and subchondral bone histomorphometry. Four histomorphometric parameters were measured: bone volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb.S). Our study showed that subchondral bone from the OA group had significantly higher bone volume (54.1 +/- 10.6%) than control group (37.8 +/- 8.1%) (P < 0.01). In addition, trabecular parameters from the OA subchondral bone showed a smaller number of sparsely distributed and thicker trabecules than in control group (P < 0.05). Medial and lateral condyle from the control group did not differ significantly, while medial condyle from OA group showed a high increase of bone volume (62.8 +/- 13.3) and consecutively different trabecular parameters when compared with the lateral condyle from the same group. Also, it was shown that there are regional differences (anterior, posterior, internal, and external) in bone parameters between both condyles within both, control and OA groups. Comparison of bone parameters from three different stage of articular cartilage degeneration (Mankin score) showed that higher degree of cartilage degeneration is followed by significant changes in subchondral bone architecture. Furthermore, we have found that progression of cartilage degeneration leads to changes in bone parameters which affected deeper levels of subchondral bone. According to these results, it can be suggested that changes in histomorphometric parameters of subchondral bone are secondary to cartilage damage and proceed deeper into subchondral bone with increasing cartilage degeneration.     

Articular Cartilage Degradation and Aberrant Subchondral Bone Remodeling in Patients with Osteoarthritis and Osteoporosis

Osteoarthritis (OA) and osteoporosis (OP) are two skeletal disorders associated with joint structures. Occasionally, OA and OP occur in the same patient. However, the effect of OP changes on OA progression in patients with osteoporotic OA (OP-OA) has not been reported, especially the potential association between subchondral bone and articular cartilage. Thus we investigated the alterations in the microstructure, biomechanical properties, and remodeling of subchondral bone as well as their association with cartilage damage in the hip joint of patients with OP-OA. Thirty-nine femoral head specimens were obtained from patients who underwent total hip arthroplasty (OA group, n = 19; OP-OA group, n = 20), and healthy specimens from cadaver donors were used (control group, n = 10). The microstructure and biomechanical properties of subchondral bone were evaluated by micro–computed tomography and micro–finite-element analysis. Histology, histomorphometric measurements, and immunohistochemistry were used to assess subchondral bone remodeling and cartilage damage. Linear regression analysis was performed to elucidate the relationship between subchondral bone and articular cartilage. In the subchondral bone of the OP-OA group, compared with that of the OA group, aberrant bone remodeling leads to an inferior microstructure and worsening biomechanical properties, potentially affecting transmission of loading stress from the cartilage to the subchondral bone, and then resulting in accelerated OA progression in patients with OP-OA. The results indicate that changes in subchondral bone could affect OA development and the improvement in subchondral bone with bone-metabolism agents may help mitigate OA progression when OP and OA coexist in the same patients. © 2019 American Society for Bone and Mineral Research.     

Treatment with recombinant lubricin attenuates osteoarthritis by positive feedback loop between articular cartilage and subchondral bone in ovariectomized rats

Osteoarthritis (OA) is a most commonly multifactorial degenerative joint disease along with the aging population, particularly in postmenopausal women. During the onset of OA, articular cartilage and subchondral bone act in concert as a functional unit. This present study is to investigate the effects of early or late treatment with recombinant lubricin on the onset of osteoarthritis (OA) in ovariectomized (OVX) rats. We found that both early and late recombinant lubricin treatments attenuated the onset of OA by positive feedback loop between articular cartilage and subchondral bone, although late treatment contributed to a lesser effect compared with early treatment. Specifically, treatment with recombinant lubricin protected articular cartilage from degeneration, demonstrated by lower proteoglycan loss, lower OARSI scores, less calcification cartilage zone and reduced immunostaining for collagen X (Col X) and matrix metalloproteinase (MMP-13) but increased the expression of lubricin, in comparison with vehicle-treated OVX rat group. Further, chondroprotective effects of lubricin normalized bone remodeling in subchondral bone underneath. It's suggested that treatment with recombinant lubricin inhibited the elevation of TRAP and Osterix positive cells in OVX rats and led to the normalization of subchondral bone microarchitectures with the suppression of subsidence of bone volume ratio (BV/TV) and trabecular thickness (Tb.Th) and the increase of trabecular separation (Tb.Sp) in vehicle-treated OVX rats. What's more, the normalization of subchondral bone in turn attenuated the articular cartilage erosion by inhibiting vascular invasion from subchondral bone to calcified cartilage zone, exemplified by inhibiting the elevation of CD31 positive cells in calcified cartilage and angiography in subchondral bone. Together, these results shed light that both early and late recombinant lubricin treatments attenuate the onset of OA by balancing the interplay between articular cartilage and subchondral bone in OVX rats, while also providing a further rationale for its therapeutic targeting to postmenopausal OA and suggesting that treatment timing is a pivotal factor for better effect acquisition.     

Comparative study of iliac crest and subchondral femoral bone in osteoarthritic patients.

This is a study of trabecular bone changes in selected regions of the femoral head. Iliac crest bone from osteoarthritic (OA) and control groups is compared to the bone from regions in the femoral head. The regions are the subchondral principal compressive and tensile areas. These areas of highest and lowest stress undergo dramatic change with OA. The compressive region has total cartilage loss and eburnation. Bone histomorphometry was done on undecalcified tissue sections stained by the von Kossa silver method and counter-stained with haematoxylin and eosin. Iliac crest histomorphometry is similar for the OA and control groups. The femoral trabecular structure in the stress regions changes in opposing directions with OA. In the compressive region the structural variables (BV/TV and BS/TV) increase [corrected], and in the tensile region decrease. Femoral bone turnover indices (OV/TV, OS/BS, and ES/BS) are no different, but femoral bone structure is different from that of the iliac crest. In OA patients there is no significant increase in iliac crest trabecular bone volume. The iliac crest is not useful to assess the bony changes in femoral OA.     

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     

Osteoblast-Chondrocyte Interactions in Osteoarthritis

There is now general agreement that osteoarthritis (OA) involves all structures in the affected joint, culminating in the degradation of the articular cartilage. It is appropriate to focus particularly on the subchondral bone because characteristic changes occur in this tissue with disease progression, either in parallel, or contributing to, the loss of cartilage volume and quality. Changes in both the articular cartilage and the subchondral bone are mediated by the cells in these two compartments, chondrocytes and cells of the osteoblast lineage, respectively, whose primary roles are to maintain the integrity and function of these tissues. In addition, altered rates of bone remodeling across the disease process are due to increased or decreased osteoclastic bone resorption. In the altered mechanical and biochemical environment of a progressively diseased joint, the cells function differently and show a different profile of gene expression, suggesting direct effects of these external influences. There is also ex vivo and in vitro evidence of chemical crosstalk between the cells in cartilage and subchondral bone, suggesting an interdependence of events in the two compartments and therefore indirect effects of, for example, altered loading of the joint. It is ultimately these cellular changes that explain the altered morphology of the cartilage and subchondral bone. With respect to crosstalk between the cells in cartilage and bone, there is evidence that small molecules can transit between these tissues. For larger molecules, such as inflammatory mediators, this is an intriguing possibility but remains to be demonstrated. The cellular changes during the progression of OA almost certainly need to be considered in a temporal and spatial manner, since it is important when and where observations are made in either human disease or animal models of OA. Until recently, comparisons have been made with the assumption, for example, that the subchondral bone is behaviorally uniform, but this is not the case in OA, where regional differences of the bone are evident using magnetic resonance imaging (MRI). Nevertheless, an appreciation of the altered cell function during the progression of OA will identify new disease modifying targets. If, indeed, the cartilage and subchondral bone behave as an interconnected functional unit, normalization of cell behavior in one compartment may have benefits in both tissues.     

Alendronate protects against articular cartilage erosion by inhibiting subchondral bone loss in ovariectomized rats

Osteoporosis (OP) and osteoarthritis (OA) are major health problems in the increasing elderly population, particularly in postmenopausal women, but their relationship remains unclear. The present study investigated whether alendronate (ALN), a potent inhibitor of bone resorption, could protect articular cartilage from degeneration in a combined animal model of OP and OA induced by ovariectomy (OVX). Seventy-eight seven-month-old female Sprague–Dawley rats were assigned into five experimental groups: (1) sham-operated with vehicle treatment, (2) sham-operated with ALN treatment, (3) OVX with vehicle treatment, (4) ALN treatment starting at OVX, and (5) ALN treatment starting at eight weeks after OVX. Histological and micro-CT analyses, together with urine collagen degradation markers, indicated that early ALN treatment completely prevented both subchondral bone loss and cartilage surface erosion induced by OVX. Although late ALN treatment also inhibited subchondral bone loss and significantly reduced cartilage erosion in the OVX rats, these tissues did not completely recover even after 10-weeks of ALN treatment. Quantitative RT-PCR analyses showed that the protective effect of ALN correlated with increased ratio of OPG/RANKL in both subchondral bone and cartilage. Moreover, whereas OVX caused upregulation of expression of matrix metalloproteinases MMP-13 and MMP-9 in the articular cartilage and chondrocytes in the interface between the articular cartilage and subchondral bone, respectively, early ALN treatment blocked whereas late ALN treatment attenuated the upregulation of these catabolic enzymes in the corresponding tissues. Together, these data indicate that the subchondral bone loss plays an important role in OA pathogenesis in the combined OP and OA model and suggest that treatment timing is an important factor for the effectiveness of anti-resorptive drug therapy of combined OP and OA.     

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.