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发育性髋关节发育不良所致原发性和继发性髋关节骨关节炎患者的股骨和髋臼间充质干细胞和祖细胞群体的特征。

Distinctiveness of Femoral and Acetabular Mesenchymal Stem and Progenitor Populations in Patients with Primary and Secondary Hip Osteoarthritis Due to Developmental Dysplasia.

机构信息

Department of Orthopaedic Surgery, University Hospital Center Zagreb, 10000 Zagreb, Croatia.

Laboratory for Molecular Immunology, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia.

出版信息

Int J Mol Sci. 2024 May 9;25(10):5173. doi: 10.3390/ijms25105173.

Abstract

Primary hip osteoarthritis (pOA) develops without an apparent underlying reason, whereas secondary osteoarthritis arises due to a known cause, such as developmental dysplasia of the hips (DDH-OA). DDH-OA patients undergo total hip arthroplasty at a much younger age than pOA patients (50.58 vs. 65 years in this study). Recently, mesenchymal stem and progenitor cells (MSPCs) have been investigated for the treatment of osteoarthritis due to their immunomodulatory and regenerative potential. This study identified cells in subchondral bone expressing common MSPC markers (CD10, CD73, CD140b, CD146, CD164, CD271, GD2, PDPN) in vivo and compared the proportions of these populations in pOA vs. DDH-OA, further correlating them with clinical, demographic, and morphological characteristics. The differences in subchondral morphology and proportions of non-hematopoietic cells expressing MSPC markers were noted depending on OA type and skeletal location. Bone sclerosis was more prominent in the pOA acetabulum (Ac) in comparison to the DDH-OA Ac and in the pOA Ac compared to the pOA femoral head (Fh). Immunophenotyping indicated diagnosis-specific differences, such as a higher proportion of CD164+ cells and their subsets in DDH-OA, while pOA contained a significantly higher proportion of CD10+ and GD2+ cells and subsets, with CD271+ being marginally higher. Location-specific differences showed that CD271+ cells were more abundant in the Fh compared to the Ac in DDH-OA patients. Furthermore, immunohistochemical characterization of stromal bone-adjacent cells expressing MSPC markers (CD10, CD164, CD271, GD2) in the Ac and Fh compartments was performed. This research proved that immunophenotype profiles and morphological changes are both location- and disease-specific. Furthermore, it provided potentially effective targets for therapeutic strategies. Future research should analyze the differentiation potential of subsets identified in this study. After proper characterization, they can be selectively targeted, thus enhancing personalized medicine approaches in joint disease management.

摘要

原发性髋骨骨关节炎(pOA)的发生没有明显的潜在原因,而继发性骨关节炎则是由于已知原因引起的,例如髋关节发育不良(DDH-OA)。DDH-OA 患者比 pOA 患者更早地接受全髋关节置换术(50.58 岁比本研究中的 65 岁)。最近,间充质干细胞和祖细胞(MSPCs)因其免疫调节和再生潜力而被用于治疗骨关节炎。本研究在体内鉴定了表达常见 MSPC 标志物(CD10、CD73、CD140b、CD146、CD164、CD271、GD2、PDPN)的软骨下骨细胞,并比较了 pOA 与 DDH-OA 之间这些细胞群体的比例,进一步将其与临床、人口统计学和形态学特征相关联。根据 OA 类型和骨骼位置,注意到软骨下形态和表达 MSPC 标志物的非造血细胞比例的差异。与 DDH-OA Ac 相比,pOA Ac 中骨硬化更为明显,与 pOA Ac 相比,pOA Ac 中骨硬化更为明显,pOA Ac 中骨硬化更为明显,pOA Ac 中骨硬化更为明显。免疫表型分析表明存在诊断特异性差异,例如 DDH-OA 中 CD164+细胞及其亚群的比例较高,而 pOA 中 CD10+和 GD2+细胞及其亚群的比例显著较高,CD271+细胞的比例略高。位置特异性差异表明,在 DDH-OA 患者中,与 Ac 相比,Fh 中 CD271+细胞更为丰富。此外,还对 Ac 和 Fh 腔室中表达 MSPC 标志物(CD10、CD164、CD271、GD2)的基质骨邻近细胞进行了免疫组织化学特征分析。这项研究证明了免疫表型谱和形态变化都是位置和疾病特异性的。此外,它为治疗策略提供了潜在的有效靶点。未来的研究应该分析本研究中鉴定的亚群的分化潜力。经过适当的表征后,它们可以被选择性地靶向,从而增强关节疾病管理中的个性化医学方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/277c/11121609/034e13f4e44e/ijms-25-05173-g001.jpg

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