Li Yunfei, Liem Yulia, Zamli Zaitunnatakhin, Sullivan Niall, Dall'Ara Enrico, Ahmed Haroon, Sellers Grace Matilda, Blom Ashley, Sharif Mohammed
Musculoskeletal Research Unit, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol BS10 5NB, UK.
Department of Biomedical Science, Kulliyyah of Allied Health Sciences, International Islamic University Malaysia, Kuantan 25200, Pahang, Malaysia.
Biomedicines. 2021 Nov 1;9(11):1593. doi: 10.3390/biomedicines9111593.
The purpose of this study was to investigate the relationship between the expression of key degradative enzymes by chondrocytes and the microarchitectural and mineral properties of subchondral bone across different stages of cartilage degradation in human hip osteoarthritis (OA).
Osteochondral samples at different stages of cartilage degradation were collected from 16 femoral heads with OA. Osteochondral samples with normal cartilage were collected from seven femoral heads with osteoporosis. Microcomputed tomography was used for the investigation of subchondral bone microarchitecture and mineral densities. Immunohistochemistry was used to study the expression and distribution of MMP13 and ADAMTS4 in cartilage.
The microarchitecture and mineral properties of the subchondral plate and trabecular bone in OA varied with the severity of the degradation of the overlying cartilage. Chondrocytes expressing MMP13 and ADAMTS4 are mainly located in the upper zone(s) of cartilage regardless of the histopathological grades. The zonal expression of these enzymes in OA (i.e., the percentage of positive cells in the superficial, middle, and deep zones), rather than their overall expression (the percentage of positive cells in the full thickness of the cartilage), exhibited significant variation in relation to the severity of cartilage degradation. The associations between the subchondral bone properties and zonal and overall expression of these enzymes in the cartilage were generally weak or nonsignificant.
Phenotypic changes in chondrocytes and remodelling of subchondral bone proceed at different rates throughout the process of cartilage degradation. Biological influences are more important for cartilage degradation at early stages, while biomechanical damage to the compromised tissue may outrun the phenotypic change of chondrocytes and is critical in the advanced stages.
本研究旨在探讨人类髋关节骨关节炎(OA)不同软骨降解阶段软骨细胞中关键降解酶的表达与软骨下骨微结构和矿物质特性之间的关系。
从16个患有OA的股骨头中收集不同软骨降解阶段的骨软骨样本。从7个患有骨质疏松症的股骨头中收集软骨正常的骨软骨样本。采用微型计算机断层扫描技术研究软骨下骨的微结构和矿物质密度。采用免疫组织化学方法研究基质金属蛋白酶13(MMP13)和含血小板反应蛋白基元的解聚素样金属蛋白酶4(ADAMTS4)在软骨中的表达和分布。
OA中软骨下板和小梁骨的微结构和矿物质特性随上方软骨降解的严重程度而变化。无论组织病理学分级如何,表达MMP13和ADAMTS4的软骨细胞主要位于软骨的上层区域。这些酶在OA中的区域表达(即表层、中层和深层区域阳性细胞的百分比),而非其整体表达(软骨全层阳性细胞的百分比),与软骨降解的严重程度呈现出显著差异。软骨下骨特性与这些酶在软骨中的区域和整体表达之间的关联通常较弱或无显著意义。
在软骨降解过程中,软骨细胞的表型变化和软骨下骨的重塑以不同速率进行。在早期阶段,生物学影响对软骨降解更为重要,而在晚期阶段,受损组织的生物力学损伤可能超过软骨细胞的表型变化,这一点至关重要。