title: Interleukin-17A increases leptin production in human bone marrow mesenchymal stem cells.
abstract: Lineage commitment of human bone marrow mesenchymal stem cells (hBM-MSCs) to adipocytes or osteoblasts has been suggested as a model system to study the relationship between type II diabetes and abnormal bone metabolism. Leptin and IL-17A inhibit adipogenesis whereas they promote osteogenesis in MSCs. Due to pathophysiologic roles of IL-17A in human metabolic diseases and bone metabolism, it was evaluated whether IL-17A-dependent inverse regulation on adipogenesis and osteogenesis was related to endogenous leptin production in hBM-MSCs. In the analysis of adiponectin and leptin secretion profiles of hBM-MSCs in response to various combinations of differentiation inducing factors, it was found that dexamethasone, a common molecule used for both adipogenesis and osteogenesis, increased leptin production in hBM-MSCs. Importantly, the level of leptin production during osteogenesis in hBM-MSCs was higher than that during adipogenesis, implicating a significant leptin production in extra-adipose tissues. IL-17A increased leptin production in hBM-MSCs and also under the condition of osteogenesis. In spite of direct inhibition on adipogenesis, IL-17A up-regulated leptin production in hBM-MSC-derived adipocytes. Anti-leptin antibody treatment partially antagonized the IL-17A dependent inhibition of adipogenesis in hBM-MSCs, suggesting a role of leptin in mediating the inverse regulation of IL-17A on osteogenesis and adipogenesis in hBM-MSCs. Therefore, the IL-17A-induced leptin production may provide a key clue to understand a molecular mechanism on the lineage commitment of hBM-MSCs into adipocytes or osteoblasts. In addition, leptin production in extra-adipose tissues like MSCs and osteoblasts should be considered in future studies on leptin-associated human diseases.
authors.affiliation: College of Pharmacy, Ajou University, Suwon, Gyeounggi-do 443-749, Republic of Korea. minsoo@alum.mit.edu
authors.forename: Minsoo
authors.initials: M
authors.lastname: Noh
mesh_terms: D015056:1-Methyl-3-isobutylxanthine; D017667:Adipocytes; D050156:Adipogenesis; D052242:Adiponectin / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism*; D002454:Cell Differentiation; D002839:Chromans / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents; D007328:Insulin / Q000494:pharmacology; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D010006:Osteoblasts; D010012:Osteogenesis; D045162:Thiazolidinediones / Q000494:pharmacology; D000077288:Troglitazone; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D052242:Adiponectin; D002839:Chromans; D005938:Glucocorticoids; D007004:Hypoglycemic Agents; C508717:IL17A protein, human; D007328:Insulin; D020381:Interleukin-17; D020738:Leptin; D045162:Thiazolidinediones; D003907:Dexamethasone; D000077288:Troglitazone; D015056:1-Methyl-3-isobutylxanthine