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A4.09 Adipokines affect differentiation of osteoarthritis and osteoporosis spongiosa-derivedmesenchymal stromal cells
  1. L Tsiklauri1,
  2. J Werner2,
  3. KW Frommer1,
  4. U Müller-Ladner1,
  5. S Wenisch2,
  6. E Neumann1
  1. 1Justus-Liebig-University Giessen, Department of Internal Medicine and Rheumatology, Kerckhoff-Klinik, Bad Nauheim, Germany
  2. 2Justus-Liebig-University Giessen, Institute of Veterinary-Anatomy, Histology and Embryology, Clinic of Small Animals, Giessen, Germany

Abstract

Introduction Age-related bone loss and articular cartilage destruction are accompanied by increased bone marrow fat infiltration. Bone marrow adipocytes have high secretory activity including secretion of proinflammatory (eg, adipokines) and matrix-degrading (eg, matrix metalloproteinases, MMPs) proteins and may be involved in progressive bone loss observed in osteoarthritis and osteoporosis. These adipocyte-derived factors most likely influence differentiation of bone marrow-derived mesenchymal stem cells (MSCs) into osteoblasts and adipocytes. Therefore, we analysed the effects of resistin, leptin and visfatin on MSC differentiation and their distribution in bone.

Methods Spongiosa containing bone marrow from femoral heads of patients undergoing hip replacement after osteoporotic femoral neck fracture or osteoarthritis 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 and of bone samples were evaluated by real time PCR.

Results Exression of visfatin was significantly increased in osteoporotic bone (n = 10) compared to non-osteoporotic bone (n = 11). Higher expression of leptin was also visible in osteoporotic bone. MSC stimulation with visfatin significantly increased MMP13 expression (eg, d21:72-fold) during adipogenic differentiation but not leptin and resistin. During osteogenic differentiation MMP2 was reduced. In contrast to adipogenic differentiation, viafatin led to reduced MMP13 expression (eg, d21:55-fold) in osteogenic differentiated cells (n = 2). Mainly visfatin decreased TIMP1 (eg, d21: 2.86-fold), TIMP2 (eg, d21: 3.17-fold), and RunX2 (eg, d21:5.85-fold) production, whereas leptin and resistin showed no effect.

Conclusion Visfatin and leptin levels were increased in osteoporotic bone tissue. Visfatin induced MMP13 expression in adipogenic cells while the production of MMP2 and MMP13 was reduced during osteogenic differentiation. The altered MMP production mediated by visfatin might influence bone remodelling at the adipose tissue/bone interface. Moreover, high levels of leptin in the osteoporotic bone might promote bone degradation. Although leptin had no local effect on MSCs differentiation in vitro, it may promote bone degradation by affecting other cell types.

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