Objective

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.

Design

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.

Results

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 CD45⁺CD3⁺ 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.

Conclusion

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.

中文翻译：

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髋骨关节炎患者髋臼和股骨骨髓的免疫和干细胞区室

客观的

髋骨关节炎 (OA) 影响骨软骨单元的所有组成部分，导致骨髓 (BM) 病变，以及对 BM 细胞功能的未知后果。我们分析了与髋关节 OA 患者获得的近端股骨干相比，受 OA 影响的髋臼中的细胞组成，以揭示尚未探索的免疫和干细胞区室。

设计

结合流式细胞术、细胞分析和转录分析，我们对来自 18 名髋关节 OA 患者的髋臼 BM 细胞进行了广泛的离体表型分析，并将它们与来自患者匹配的股骨干 BM 样本的对应物进行了比较。结果与骨骼部位和年龄的差异有关。

结果

与股骨BM相比，髋臼BM具有更高频率的T淋巴细胞、非造血细胞和集落形成单位成纤维细胞潜能。随着患者年龄的增长，髋臼 CD45 ⁺ CD3 ⁺ T 淋巴细胞的发生率增加（95% CI：0.1770 至 0.0.8416），而克隆造血祖细胞下降（95% CI：-0.9023 至 -0.2399）。另一方面，在股骨 BM 中，我们观察到更高的 B 淋巴细胞、骨髓和红细胞频率。髋臼间充质基质细胞 (MSCs) 显示出与存活和炎症相关基因的表达相关的衰老特征。在髋臼 MSCs 中检测到有效的成骨和软骨形成分化，而在其股骨对应物中脂肪生成更为明显。

结论

我们的研究结果表明，BM 细胞区室和 MSC 的差异可能是由于 OA 压力微环境的影响，但也不能排除髋臼与股骨干特异性特征。这些结果带来了关于髋臼 BM 细胞群的新知识，并且可以作为 OA 的新致病机制和治疗靶点来解决。