gms | German Medical Science

Background: Osteoporosis predominantly affects elderly people and is characterized by bone loss, increased fracture risk and reduced regeneration ability. Age-related bone loss correlates with increased bone marrow adiposity due to a shift of osteogenic towards adipogenic differentiation of bone marrow mesenchymal stem cells (MSC). Adipose tissue is metabolically active: It releases proinflammatory (e.g. adipokines) and matrix-degrading proteins (e.g. MMPs), which directly promote bone loss. Therefore, adipocyte-derived factors might influence differentiation of MSC. We analyzed the expression of adipokines (visfatin, resistin and leptin) in bone tissue and their effects on MSC adipogenic differentiation.

Methods: RNA and MSC were isolated out of spongiosa from femoral heads (hip replacement surgery of osteoarthritis patients or after osteoporotic femoral neck fracture). Adipogenic differentiation was performed with/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. Proinflammatory factors were measured by ELISA.

Results: Visfatin and leptin levels were increased in OP bone vs. non-osteoporotic OA bone while resistin was reduced. Visfatin induced the secretion of proinflammatory factors (IL-6, IL-8, MCP-1) during adipogenic differentiation under standard cell culture conditions (e.g IL6, 21d control: 270.3±140.2 pg/ml; visfatin: 3,227±600.4 pg/ml, p=0.0006; n=12) as well as on purified cancellous bone (e.g. IL-6, 21d control: 789±54.04 pg/ml; visfatin: 1,855±266 pg/ml, p=0.038; n=7) but was markedly reduced during differentiation on spongiosa. Visfatin significantly induced MMP13 mRNA (e.g. 21d: 81-fold/p=0.0005; n=12) as well as protein expression (e.g. 21d control: 179.9±64.04 pg/ml; visfatin: 10,725±4266 pg/ml, p=0.0005; n=12) during adipogenic differentiation under standard culture conditions; however visfatin-induced MMP13 expression was reduced during adipogenesis on spongiosa (e.g. 21d: 13.4-fold/p=0.015, n=7). Regarding MMP2 expression, visfatin also led to elevated expression of MMP2 (e.g. 21d: 5-fold/p=0.0053; n=6) during adipogenic differentiation in culture, while during adipogenesis on spongiosa enhancement of MMP2 by visfatin was not visible.

Conclusion: Visfatin and leptin levels were elevated in osteoporotic bone. Therefore, visfatin-mediated increase of MMPs and proinflammatory cytokines during adipogenic differentiation might influence bone turnover at the adipose tissue/bone interface. Our results suggested that adhesion of MSC to extracellular matrix of spongiosa attenuated visfatin mediated detrimental effects during adipogenesis.