Obese Adipose Tissue Secretome leads to increased osteoclast differentiation in vitro by enhancing osteoclastogenic receptors expression and lipid metabolism on osteoclast precursors

INTRODUCTION: The pathological adipose tissue (AT) accumulation in obesity, can interfere with bone remodeling, unbalancing osteoblasts and osteoclasts (OSTCs) activities. The increased availability of circulant free fatty acids and osteoclastogenic cytokines, as RANK-L and M-CSF, released during obesity, may favor the formation of OSTCs (monocytic-differentiated multinucleated cells responsible for bone-resorption) leading to bone loss. OBJECTIVE: We aimed to evaluate the effect of the secretome derived from AT of patients with obesity (OATS) or lean (LATS) on the OSTCs differentiation. METHODS: The study approved by HUPE-UERJ ethics committee (CAAE: 56302121.2.0000.5259). Peripheral blood monocytes isolated from lean or obese donors; Multinucleated cells TRAP+/DAPI quantified by microscopy; Osteoclastogenic receptors (RANK and CSFR1), bone resorption (cathepsin K, integrin β3, and MMP9) and lipid metabolism markers (CPT1C and CD36) assessed by western blot. RESULTS: Comparing to eutrophics, the monocytes from obesity-bearing patients showed higher expression of RANK, CSFR1, CD36 and CPT1C, which positively correlated with BMI. Treatment of macrophages derived from lean human monocytes with OATS enhanced the expression of the same markers. During OSTCs differentiation, treatment of macrophages with OATS, comparing to LATS, increased TRAP activity and the formation of TRAP+ multinucleated cells. The greater OSTCs formation correlated with the BMI. Treatment with OATS increased the expression of bone resorption and lipid metabolism markers. CONCLUSION: Monocytes from patients with obesity have greater capacity to differentiate into OSTCs. During obesity, factors secreted by AT increase lipid metabolism and osteoclastogenic receptors in OSTCs precursors improving OSTCs differentiation and their resorptive capacity in vitro. Financial support: CNPq, DECIT-SUS and FAPERJ.