Effect of recombinant irisin on recombinant human bone morphogenetic protein-2 induced osteogenesis and osteoblast differentiation.

Yohei Ohyama, Yoichi Ohta, Ryo Sugama, Yukihide Minoda, Sho Masuda, Hidetomi Terai, Hiroaki Nakamura

Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Japan; Department of Orthopaedic Surgery, Osaka Metropolitan University Graduate School of Medicine, Japan.Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Japan; Department of Orthopaedic Surgery, Osaka Metropolitan University Graduate School of Medicine, Japan. · pubmed

Paper

Abstract

Osteoporotic fragility fractures substantially impact aging societies, necessitating long-term care and increasing healthcare costs. Myokine irisin, secreted by skeletal muscle, influences bone metabolism; however, a comprehensive understanding of the mechanisms by which irisin affects bone metabolism is still lacking. Therefore, this study aimed to explore the effects of irisin on osteogenesis and osteoblast differentiation triggered by bone morphogenetic protein-2 (BMP-2). We used 4-week-old male ICR mice and implanted polyethylene glycol pellets containing recombinant human BMP-2 (rh-BMP-2) into the left dorsal muscle pouch. Mice received weekly intraperitoneal injections of either phosphate-buffered saline or recombinant irisin (re-irisin). Ectopic bone formation was evaluated 3 weeks post-surgery using micro-computed tomography (μ-CT) and histological analysis. In vitro experiments, C2C12 cells were treated with or without rh-BMP-2 and re-irisin, and we assessed osteoblast differentiation markers, e.g., runt-related transcription factor 2, alkaline phosphatase, osteocalcin, and osteopontin, using real-time reverse transcription-polymerase chain reaction. The μ-CT analyses showed that re-irisin significantly increased bone mineral content and bone volume of ectopic bones newly formed by rh-BMP-2. The gene expressions of the osteoblast markers were significantly increased by rh-BMP-2 and further upregulated by re-irisin. The treatment of cyclic AMP response element-binding protein (CREB) small interfering RNA attenuated these effects, suggesting that CREB signaling pathway was involved in rh-BMP-2/re-irisin-induced osteoblastic differentiation. This study demonstrates the potential of irisin to enhance osteogenesis through BMP signaling, offering insights for osteoporosis treatment and highlighting irisin as a promising therapeutic target for improving bone health and extending a healthy lifespan.

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Research summary

The paper investigates the role of irisin in enhancing osteogenesis and osteoblast differentiation, which is relevant to bone health and osteoporosis—a condition that significantly affects aging populations. However, while it offers insights into potential therapeutic targets for improving bone health, the findings are incremental and do not address the root causes of aging or lifespan extension directly. Thus, the impact is solid but limited.

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