Background/Purpose:

Osteoporosis predominantly affects elderly people and is characterized by bone loss, increased fracture risk and reduced regeneration ability. An inverse relationship between bone marrow adipose tissue and bone mineral density in osteoporosis and during aging is well documented, but the role of fat–bone interactions in the pathogenesis of osteoporosis is poorly understood. Adipose tissue is metabolically highly active. Adipokines (e.g. visfatin, resistin and leptin) are adipocyte-derived factors with immunomodulatory properties and they might influence the differentiation of bone marrow-derived mesenchymal stem cells (MSC) into osteoblasts and adipocytes. Thus, the presence of adipokines in bone tissue of femoral heads and their effects on MSC differentiation were analyzed.

Methods: RNA and MSC were isolated from spongiosa of femoral heads derived from hip replacement surgery of osteoarthritis patients or after osteoporotic femoral neck fracture. Adipogenic as well as osteogenic MSC differentiation was performed with and without adipokines. For the transfer and differentiation of MSC on cancellous bone, bone fragments were purified and sterilized. Gene expression was evaluated by Realtime PCR. Matrix mineralization was assayed using Alizarin red S staining and proinflammatory factors were measured by ELISA.

Results:

Higher levels of visfatin (FF mean 7.77±1.86, n=11; OA 2.25±0.36, n=13) and leptin (FF mean 21.98±5.41, n=11; OA 15.86±3.93, n=12) could be detected in osteoporotic (FF) bone compared to non-osteoporotic (OA) bone, however resistin was reduced in FF (FF mean 7.73±2.95, n=9; OA 34.28±9.27, n=12). Visfatin induced the secretion of proinflammatory factors (IL-6, IL-8, MCP-1 and GRO-a) during both, osteogenic and adipogenic differentiation. Significantly increased matrix mineralization (visfatin: 82%±28%, control: 3.9%±1.8%; n=3) and downregulated collagen type 1 expression (e.g. d21: -4.6-fold, n=7) were detected in osteogenically differentiated cells after visfatin stimulation. In contrast to leptin and resistin, visfatin reduced the expression of MMP2, MMP13, TIMP1 and TIMP2 (e.g. d21: -2.4-fold / -3.18-fold / -3.2-fold / -4.3 fold, respectively) during osteogenic differentiation. The expression of MMP13 (e.g. d21: 104-fold, n=9) and MMP2 (e.g. d21: 5.1-fold, n=9) was significantly enhanced after stimulation with visfatin during adipogenic differentiation under standard cell culture conditions, however visfatin-mediated MMP13 expression (e.g. d21: 13.8-fold, n=7) as well as induction of IL-6 and IL-8 release was markedly reduced during differentiation on purified autologous cancellous bone.

Conclusion: The results support the hypothesis that adipokines, especially the visfatin-mediated increase of matrix mineralization and reduction of collagen type 1 expression might lead to enhanced bone fragility and contribute to the pathogenesis of osteoporosis. Moreover visfatin-induced release of proinflammatory cytokines and dysregulated expression of MMPs and TIMPs during MSC-differentiation might influence bone turnover at the adipose tissue/bone interface

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/influence-of-adipokines-on-the-differentiation-of-spongiosa-derived-mesenchymal-stromal-cells-from-osteoporosis-and-osteoarthritis-patients/