Adiponectin Inhibits the Differentiation and Maturation of Osteoclasts Via mTOR Pathway in Multiple Myeloma

Abstract

Background: To investigate the correlation of adipose cytokines (visfatin, leptin, and adiponectin) with multiple myeloma bone disease (MBD) and explore the effects and mechanism of adiponectin on the differentiation and maturation of osteoclasts in multiple myeloma (MM). Methods: The levels of visfatin, leptin and adiponectin were measured .Their relationships between the index of myeloma tumor load and bone disease were analyzed. RT-PCR was used to detect the expressions of RANKL, OSCAR, TRAP and Cathepsin K genes. Flow cytometry (FCM) was used to detect the expressions of AdipoR1 and phosphorylation of mTOR pathway related proteins mTOR and 4EBP1. Results :There were no significant linear correlation between leptin, visfatin and the indexes of myeloma tumor load and bone disease. Serum adiponectin levels were significantly higher in newly diagnosed multiple myeloma patients and negatively linear correlated with β2-microglobulin.There is a positive linear correlation relationship between the adiponectin and osteocalcin. The number of maturation osteoclasts in adiponectin group was less than the control group. Adiponectin also inhabits the mRNA level of osteoclast related factor- RANKL, OSCAR, TRAP and Cathepsin K. Flow cytometry showed that adiponectin increased the expression of AdipoR1 on the surface of osteoclast precursor((26.21±4.27)% vs (29.86±6.23)%, p<0.05) and reduced the expression of p-mTOR ((7.89±1.00)% vs (5.91±1.26)%, p<0.05) and p-4EBP1 ((26.78±5.00)% vs (22.49±4.24)%, p<0.05). Conclusion: Adiponectin inhibits the differentiation and maturation of osteoclasts via increasing the expression of AdipoR1 and reducing the phosphorylation levels of mTOR and 4EBP1 proteins in MM patients. Disclosures No relevant conflicts of interest to declare.