tailieunhanh - Báo cáo y học: "Local leptin production in osteoarthritis subchondral osteoblasts may be responsible for their abnormal phenotypic expression"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài: Local leptin production in osteoarthritis subchondral osteoblasts may be responsible for their abnormal phenotypic expression. | Mutabaruka et al. Arthritis Research Therapy 2010 12 R20 http content 12 1 R20 RESEARCH ARTICLE Open Access Local leptin production in osteoarthritis subchondral osteoblasts may be responsible for their abnormal phenotypic expression Marie-Solange Mutabaruka21 Mohamed Aoulad Aissat1 Aline Delalandre 1 Martin Lavigne2 and Daniel Lajeunesse 1 Abstract Introduction Leptin is a peptide hormone with a role in bone metabolism and rheumatic diseases. The subchondral bone tissue plays a prominent role in the pathophysiology of osteoarthritis OA related to abnormal osteoblast Ob differentiation. Although leptin promotes the differentiation of Ob under normal conditions a role for leptin in OA Ob has not been demonstrated. Here we determined if endogenous leptin produced by OA Ob could be responsible for the expression of the abnormal phenotypic biomarkers observed in OA Ob. Methods We prepared primary normal and OA Ob from subchondral bone of tibial plateaus removed for knee surgery of OA patients or at autopsy. We determined the production of leptin and of the long biologically active leptin receptors OB-Rb using reverse transcriptase-polymerase chain reaction ELISA and Western blot analysis. We determined the effect of leptin on cell proliferation by BrdU incorporation and 3- 4 5-Dimethylthiazol-2-yl -2 5-diphenyltetrazolium bromide MTT assays and we determined by Western blot analysis phospho 42 44 MAPK p42 44 2 and phospho p38 levels. We then determined the effect of the addition of exogenous leptin leptin receptor antagonists inhibitors of leptin signaling or siRNA techniques on the phenotypic features of OA Ob. Phenotypic features of Ob were determined by measuring alkaline phosphatase activity ALP osteocalcin release OC collagen type 1 production CICP and of Transforming Growth Factor-p1 TGF-P1 . Results Leptin expression was increased approximately five-fold and protein levels approximately two-fold in OA Ob compared to normal. Leptin .