IZKF Group Tissue Regeneration in Musculoskeletal Diseases, University Hospital Wuerzburg, Wuerzburg, Bavaria, 97070, Germany; Bernhard-Heine-Center for Locomotion Research, University Wuerzburg, Wuerzburg, Bavaria, 97070, Germany.
Bernhard-Heine-Center for Locomotion Research, University Wuerzburg, Wuerzburg, Bavaria, 97070, Germany.
Osteoarthritis Cartilage. 2022 Aug;30(8):1116-1129. doi: 10.1016/j.joca.2022.05.001. Epub 2022 May 13.
Hip osteoarthritis (OA) affects all components of the osteochondral unit, leading to bone marrow (BM) lesions, and unknown consequences on BM cell functionality. We analyzed the cellular composition in OA-affected acetabula compared to proximal femur shafts obtained of hip OA patients to reveal yet not explored immune and stem cell compartments.
Combining flow cytometry, cellular assays and transcription analyses, we performed extensive ex vivo phenotyping of acetabular BM cells from 18 hip OA patients, comparing them with their counterparts from patient-matched femoral shaft BM samples. Findings were related to differences in skeletal sites and age.
Acetabular BM had a greater frequency of T-lymphocytes, non-hematopoietic cells and colony-forming units fibroblastic potential than femoral BM. The incidence of acetabular CD45CD3 T-lymphocytes increased (95% CI: 0.1770 to 0.0.8416), while clonogenic hematopoietic progenitors declined (95% CI: -0.9023 to -0.2399) with age of patients. On the other side, in femoral BM, we observed higher B-lymphocyte, myeloid and erythroid cell frequencies. Acetabular mesenchymal stromal cells (MSCs) showed a senescent profile associated with the expression of survival and inflammation-related genes. Efficient osteogenic and chondrogenic differentiation was detected in acetabular MSCs, while adipogenesis was more pronounced in their femoral counterparts.
Our results suggest that distinctions in BM cellular compartments and MSCs may be due to the influence of the OA-stressed microenvironment, but also acetabular vs femoral shaft-specific peculiarities cannot be excluded. These results bring new knowledge on acetabular BM cell populations and may be addressed as novel pathogenic mechanisms and therapeutic targets in OA.
髋关节骨关节炎（OA）影响骨软骨单位的所有组成部分，导致骨髓（BM）病变，并对 BM 细胞功能产生未知影响。我们分析了 OA 患者髋关节髋臼与股骨近端骨髓样本中的细胞组成，以揭示尚未探索的免疫和干细胞区室。
我们通过流式细胞术、细胞分析和转录分析，对 18 名髋关节 OA 患者的髋臼 BM 细胞进行了广泛的体外表型分析，将其与患者匹配的股骨骨髓样本进行比较。研究结果与骨骼部位和年龄的差异有关。
与股骨 BM 相比，髋臼 BM 中的 T 淋巴细胞、非造血细胞和成纤维细胞集落形成单位的频率更高。髋臼 CD45CD3 T 淋巴细胞的发生率增加（95%可信区间：0.1770 至 0.0.8416），而造血祖细胞的克隆形成能力下降（95%可信区间：-0.9023 至-0.2399）与患者年龄有关。另一方面，在股骨 BM 中，我们观察到更高的 B 淋巴细胞、髓细胞和红细胞频率。髋臼间充质基质细胞（MSCs）表现出与生存和炎症相关基因表达相关的衰老特征。在髋臼 MSC 中检测到有效的成骨和成软骨分化，而在其股骨对应物中，脂肪生成更为明显。
我们的结果表明，BM 细胞区室和 MSC 的差异可能是由于 OA 应激微环境的影响，但也不能排除髋臼与股骨干特异性的差异。这些结果为髋臼 BM 细胞群提供了新的认识，并可能作为 OA 的新发病机制和治疗靶点。
