Irisin fails to rescue bone loss in a rat model of chronic kidney disease – Mineral bone disorder (CKD-MBD) but interacts with parathyroid hormone in vivo and in vitro in IDG-SW3 osteocytes

Introduction Chronic kidney disease progression leads to bone loss and increased fracture and mortality risk. The myokine irisin, produced by muscle during exercise, has been shown to exert protective effects on bone in healthy animals and a potential interaction with PTH in vitro . The aims of this study were to determine the effect of irisin on bone in CKD-MBD and determine if an interaction exists with PTH in vitro and in vivo . Methods Early and mature IDG-SW3 osteocytes were treated with recombinant irisin, PTH, or both. Mineralization and osteocyte cell markers were assessed. In a similar 2 × 2 design, male Cy/+ IU (CKD-MBD) rats were treated with and without irisin under high and low PTH conditions. Dynamic histomorphometry, bone structure, mechanical properties, and musculoskeletal gene markers were assessed. Results In vitro , irisin alone downregulated Dkk1 and Sost , inhibitors of bone formation, and PTH receptor mRNA expression, primarily in early osteocytes. However, in the presence of PTH, no effects of irisin were observed. In vivo , the administration of irisin to animals with progressive CKD also downregulated PTH receptor 1 expression but did not affect bone turnover or structure or mechanical properties. Conclusions Irisin did not meaningfully ameliorate bone loss in an animal model of CKD-MBD but did interact with PTH by downregulating its receptor in vitro in osteocytes and in vivo in bone.