P123 Extracellular matrix attenuated matrix-degrading effects of visfatin during adipogenic MSC differentiation. (March 2019)

• Record Type: Journal Article
• Authors: Tsiklauri, L; Werner, J; Frommer, K; Rehart, S; Wenisch, S; Müller-Ladner, U; Neumann, E
• Is Part Of: Annals of the rheumatic diseases. Volume 78(2019)Supplement 1
• Page Start: A55
• Page End: A55
• Publication Date: 2019-03
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2018-EWRR2019.111
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Career situation of first and presenting author: Student for a master or a PhD. Introduction: Osteoporosis (OP) is the most common age-related disorder characterized by bone loss and correlates with increased bone marrow adiposity due to a shift of osteogenic towards adipogenic differentiation of bone marrow mesenchymal stem cells (MSC). Therefore, bone marrow adipocytes are in direct contact with the altered bone matrix in OP. Adipose tissue is metabolically active. Therefore, adipocyte-derived factors such as adipokines might influence MSC differentiation. Objectives: We analyzed the presence of adipokines (visfatin, resistin and leptin) in bone tissue and their effects on MSC differentiation under standard culture vs. spongiosa. Methods: RNA and MSC were isolated from spongiosa of femoral heads of osteoarthritis patients after hip replacement surgery, or after osteoporotic femoral neck fracture. Adipogenic MSC differentiation was performed with/without adipokines and visfatin inhibitor Apo866 as well as SB203580 p38-MAPK inhibitor. For the transfer and differentiation of MSC on cancellous bone, bone fragments were purified and sterilized. Gene expression was evaluated by Realtime PCR. Protein production was analyzed by ELISA. Results: Visfatin and leptin levels were increased in OP bone vs. non-osteoporotic OA bone, however, resistin was reduced. Visfatin induced the secretion of proinflammatory factors during adipogenesis in standard cell culture as well as on cancellous bone. Visfatin-induced cytokine release was markedly reduced during differentiation on spongiosa (e.g. 14d IL6, x-fold: standard culture 151±110, spong. 40±30, n=7). Significantly elevated MMP13 mRNA as well as protein expression induced by visfatin could be observed during adipogenesis in standard cell culture as well as on spongiosa, however visfatin-mediated MMP13 expression was reduced on cancellous bone (e.g. 21d, x-fold, : standard culture 81±89, spong. 13±21, n=7). The visfatin inhibitor Apo866 inhibited the visfatin-induced cytokine release. However, the MMP13 expression was not influenced during adipogenesis in culture (n=4). In contrast to Apo866, the p38-MAPK inhibitor did not reduce cytokine release during adipogenesis. Conclusions: 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 support the idea that the extracellular matrix attenuates visfatin-mediated detrimental effects during adipogenesis. The observed visfatin-mediated effects most likely depend on different signaling pathways. Disclosure of Interest: None declared.