Myostatin inhibits osteoblastic differentiation by suppressing osteocyte-derived exosomal microRNA-218: A novel mechanism in muscle-bone communication

J. Biol. Chem., 2017 · DOI: 10.1074/jbc.M116.770941 · Published: May 2, 2017

Simple Explanation

Muscle and bone communicate, but how they coordinate their actions isn't well understood. This study looks at myostatin, a protein from muscles, and its role in this communication, particularly how it affects bone cells called osteocytes. Myostatin influences osteocytes to produce more of certain bone regulators like sclerostin, DKK1, and RANKL, while reducing a specific microRNA (miR-218) in both the osteocytes and the exosomes they release. These modified exosomes, when taken up by osteoblasts (bone-forming cells), lead to a decrease in osteoblast differentiation. This inhibitory effect is reversed when miR-218 is reintroduced, suggesting miR-218's crucial role in this process.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Not specified

Key Findings

1
Myostatin increases the expression of SOST, DKK1, and RANKL in osteocytes, which are important regulators in bone remodeling.
2
Myostatin inhibits the expression of miR-218 in osteocyte-derived exosomes, suggesting a direct target of myostatin.
3
Myostatin-modified osteocytic exosomes inhibit osteoblastic differentiation by down-regulating the Wnt signaling pathway.

Research Summary

This study investigates how muscle-released products interact with bone cells to influence their function, focusing on myostatin's role in muscle-bone interaction. Myostatin directly targets osteocyte-derived exosomes to regulate the content of miR-218, inhibiting its expression in exosomes released from osteocytes. The inhibitory effect of myostatin-mediated suppression of osteocytic exosomal miR-218 on osteoblast function is associated with the down-regulation of the canonical Wnt signaling pathway.

Practical Implications

Therapeutic Target

miR-218 could be a therapeutic target for treating bone loss associated with sarcopenia, menopause, and immobilization.

Muscle-Bone Communication

The study provides a novel mechanism underlying muscle-bone communication to maintain homeostasis of the local musculoskeletal environment via osteocytes.

Dual Benefit of Myostatin Inhibition

Inhibition of myostatin may serve a dual benefit in the protection of muscle and bone against loss in osteopenia and sarcopenia.

Study Limitations

1
The manner in which myostatin is transported to the osteocyte is unclear.
2
Whether other myokines, such as irisin and IL-6, have similar direct effects to that of myostatin on the osteocyte is unknown.
3
The study supports the notion that inhibition of myostatin serves a dual benefit in the protection of muscle and bone against loss in osteopenia and sarcopenia

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