Artikel
Adipokines affect differentiation of osteoporosis and osteoarthritis spongiosa-derived mesenchymal stromal cells
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Veröffentlicht: | 29. August 2016 |
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Background: Age-related bone loss and articular cartilage damage are associated with increased bone marrow fat infiltration. A reciprocal relationship between bone marrow adiposity and bone mass has been implicated in osteoporosis. Adipose tissue is metabolically active: It releases proinflammatory (e.g. adipokines) and matrix-degrading proteins (e.g. matrix metalloproteinases, MMPs) which promote progressive bone loss. Moreover, adipocytes and osteoblasts share the same precursor, the mesenchymal stem cell (MSC). The differentiation of MSC into adipocytes or osteoblasts is an important determinant of bone structural integrity. Adipocyte-derived factors might influence differentiation of bone marrow-derived MSCs. Therefore, we analyzed the effects of resistin, leptin and visfatin on MSC-differentiation and their distribution in bone.
Methods: Spongiosa from femoral heads of osteoarthritis patients were collected. Primary spongiosa-derived mesenchymal stromal cells (hMSCs) as well as commercially obtained MSCs were cultured in adipogenic and osteogenic media 3 weeks with/without adipokines. mRNA expression of adipokines, bone marker genes, TIMPs and MMPs of stimulated hMSCs/MSCs as well as of bone samples were evaluated by real time PCR. The secretion of pro-inflammatory mediators was determined by ELISA.
Results: Expression of visfatin and leptin was significantly increased in osteoporotic bone (n=14) compared to non-osteoporotic bone (n=14). The stimulation with visfatin of hMSC during adipogenic differentiation markedly increased MMP13-expression (e.g. d21: 72-fold) but not leptin and resistin. In osteogenic differentiated cells, a reduction of MMP2 by stimulation of all adipokines could be observed (n=3). However, the expression of MMP13 was downregulated mainly by visfatin (e.g. d21: 55-fold). In addition, visfatin decreased TIMP1 (e.g. d21: 2.9-fold), TIMP2 (e.g. d21: 3.2-fold), and RunX2 (e.g. d21: 5.9-fold) production and overall matrix production in contrast to leptin and resistin during osteogenic differentiation. Moreover, visfatin induced the secretion of IL-6, IL-8 and MCP-1 in both, osteogenic and adipogenic differentiated cells.
Conclusion: Visfatin and leptin levels are increased in osteoporotic bone. The altered MMP and TIMP production mediated especially by visfatin might influence bone remodeling at the bone/bone marrow interface. Although leptin had no local effect on MSCs differentiation in vitro, it may modulate bone degradation by affecting other cell types such as inflammatory cells.