Immune and stem cell compartments of acetabular and femoral bone marrow in hip osteoarthritis patients

• Published in: Osteoarthritis and cartilage 2022-08, Vol.30 (8), p.1116-1129
• Main Authors: Trivanovic, D., Harder, J., Leucht, M., Kreuzahler, T., Schlierf, B., Holzapfel, B.M., Rudert, M., Jakob, F., Herrmann, M.
• Format: Article
• Language: English
• Subjects: Acetabulum; Aging; Bone marrow; Femur; Mesenchymal stromal cells; Osteoarthritis
• ISSN: 1063-4584; 1522-9653
• DOI: 10.1016/j.joca.2022.05.001

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 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. 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.