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Published on: February 28, 2017
Myonectin inhibits the differentiation of osteoblasts and osteoclasts in mouse cells
Miku Kawaguchi1, Naoyuki Kawao1, Yoshimasa Takafuji1
1Department of Physiology and Regenerative Medicine, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka, 589-8511, Japan.
Abstract:
Myonectin is a myokine, which is involved in the pathophysiology of diabetes and obesity, and various myokines are involved in the interactions between skeletal muscle and bone. However, roles of myonectin in bone have still remained unknown. We therefore examined the effects of myonectin on mouse osteoblast and osteoclast differentiation in vitro. Myonectin significantly suppressed the mRNA levels of osteogenic genes and alkaline phosphatase (ALP) activity in mouse osteoblasts. As for osteoclasts, myonectin significantly suppressed osteoclast formation as well as the mRNA levels of osteoclast-related genes enhanced by receptor activator nuclear factor κB ligand (RANKL) from mouse monocytic RAW264.7 cells. Moreover, myonectin significantly suppressed osteoclast formation from mouse bone marrow cells in the presence of macrophage-colony stimulating factor and RANKL. On the other hand, myonectin significantly suppressed RANKL-induced oxygen consumption rate and peroxisome proliferator-activated receptor γ coactivator-1β mRNA levels in RAW264.7 cells, although myonectin did not affect these mitochondrial biogenesis parameters in mouse osteoblasts. In conclusion, the present study demonstrated that myonectin suppresses the differentiation and ALP activity in mouse osteoblasts. Moreover, myonectin suppressed osteoclast differentiation from mouse bone marrow and RAW264.7 cells partly through an inhibition of mitochondrial biogenesis.
Insights
Myonectin, a myokine, inhibits osteoblast differentiation and activity. It also suppresses osteoclast formation by impacting mitochondrial biogenesis, revealing its role in bone health.
Area of Science:
- Bone Biology
- Endocrinology
- Skeletal Muscle Physiology
Background:
- Myonectin is a myokine implicated in diabetes and obesity.
- Myokines mediate skeletal muscle and bone interactions.
- The specific role of myonectin in bone physiology remains largely unexplored.
Purpose of the Study:
- To investigate the effects of myonectin on osteoblast differentiation.
- To examine the impact of myonectin on osteoclastogenesis.
- To elucidate the mechanisms underlying myonectin's influence on bone cells.
Main Methods:
- In vitro studies using mouse osteoblasts and RAW264.7 cells.
- Assessment of osteogenic gene expression and alkaline phosphatase (ALP) activity.
- Analysis of osteoclast formation and related gene expression induced by RANKL.
- Evaluation of mitochondrial biogenesis parameters, including oxygen consumption rate.
Main Results:
- Myonectin significantly suppressed osteoblast differentiation markers and ALP activity.
- Myonectin inhibited RANKL-induced osteoclast formation and associated gene expression.
- Myonectin reduced mitochondrial biogenesis in RAW264.7 cells, affecting oxygen consumption and PGC-1β levels.
- These mitochondrial effects were not observed in osteoblasts.
Conclusions:
- Myonectin negatively regulates osteoblast differentiation and activity.
- Myonectin impairs osteoclast differentiation, partly via inhibition of mitochondrial biogenesis.
- These findings highlight myonectin as a potential regulator of bone metabolism.
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