Osteocytic Connexin43 Channels Regulate Bone-Muscle Crosstalk.

Area of Science:

• Cellular Biology
• Skeletal Physiology
• Biomedical Science

Background:

• Bone-muscle crosstalk is vital for skeletal function and disease progression.
• Osteocyte connexin 43 (Cx43) impacts skeletal muscle, but the roles of its gap junctions (GJs) and hemichannels (HCs) are unclear.

Purpose of the Study:

• To investigate the distinct roles of Cx43-formed GJs and HCs in osteocytes on skeletal muscle.
• To elucidate the molecular mechanisms underlying Cx43-mediated bone-muscle communication.

Main Methods:

• Utilized two Cx43 osteocyte-specific transgenic mouse models (Δ130-136 and R76W) to inhibit GJs and/or HCs.
• Assessed skeletal muscle mass, protein synthesis/degradation, contractile force, and fiber type.
• Analyzed prostaglandin E2 (PGE2) levels and performed in vitro myogenesis assays using conditioned media.

Main Results:

• Inhibition of osteocyte Cx43 HCs (Δ130-136) reduced fast-twitch muscle mass, protein synthesis, and increased degradation.
• Blockage of Cx43 GJs (R76W and Δ130-136) decreased muscle contractile force and induced fast-to-slow fiber transition.
• Reduced PGE2 levels were observed in transgenic mice; PGE2 injection partially rescued muscle mass and function.

Conclusions:

• Osteocytic Cx43 HCs are critical for maintaining fast-twitch muscle mass via protein synthesis and degradation regulation.
• Osteocytic Cx43 GJs are essential for muscle contractile force and myogenesis, with PGE2 partially mediating these effects.
• Cx43 channels in osteocytes play distinct, channel-specific roles in regulating skeletal muscle homeostasis.