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Osteocytic Connexin43 Channels Regulate Bone-Muscle Crosstalk
- Source :
- Cells, Cells, Vol 10, Iss 237, p 237 (2021), Volume 10, Issue 2
- Publication Year :
- 2020
-
Abstract
- Bone&ndash<br />muscle crosstalk plays an important role in skeletal biomechanical function, the progression of numerous pathological conditions, and the modulation of local and distant cellular environments. Previous work has revealed that the deletion of connexin (Cx) 43 in osteoblasts, and consequently, osteocytes, indirectly compromises skeletal muscle formation and function. However, the respective roles of Cx43-formed gap junction channels (GJs) and hemichannels (HCs) in the bone&ndash<br />muscle crosstalk are poorly understood. To this end, we used two Cx43 osteocyte-specific transgenic mouse models expressing dominant negative mutants, &Delta<br />130&ndash<br />136 (GJs and HCs functions are inhibited), and R76W (only GJs function is blocked), to determine the effect of these two types of Cx43 channels on neighboring skeletal muscle. Blockage of osteocyte Cx43 GJs and HCs in &Delta<br />136 mice decreased fast-twitch muscle mass with reduced muscle protein synthesis and increased muscle protein degradation. Both R76W and &Delta<br />136 mice exhibited decreased muscle contractile force accompanied by a fast-to-slow fiber transition in typically fast-twitch muscles. In vitro results further showed that myotube formation of C2C12 myoblasts was inhibited after treatment with the primary osteocyte conditioned media (PO CM) from R76W and &Delta<br />136 mice. Additionally, prostaglandin E2 (PGE2) level was significantly reduced in both the circulation and PO CM of the transgenic mice. Interestingly, the injection of PGE2 to the transgenic mice rescued fast-twitch muscle mass and function<br />however, this had little effect on protein synthesis and degradation. These findings indicate a channel-specific response: inhibition of osteocytic Cx43 HCs decreases fast-twitch skeletal muscle mass alongside reduced protein synthesis and increased protein degradation. In contrast, blockage of Cx43 GJs results in decreased fast-twitch skeletal muscle contractile force and myogenesis, with PGE2 partially accounting for the measured differences.
- Subjects :
- 0301 basic medicine
hemichannels
bone–muscle crosstalk
Muscle Fibers, Skeletal
Connexin
030209 endocrinology & metabolism
Mice, Transgenic
Protein degradation
Muscle Development
Osteocytes
Bone and Bones
Dinoprostone
Article
03 medical and health sciences
0302 clinical medicine
medicine
Myocyte
Animals
lcsh:QH301-705.5
Cells, Cultured
Myogenesis
Chemistry
Muscles
Gap junction
Skeletal muscle
Gap Junctions
Cell Differentiation
General Medicine
Organ Size
Cell biology
Cx43
Sarcoplasmic Reticulum
030104 developmental biology
medicine.anatomical_structure
lcsh:Biology (General)
Osteocyte
Connexin 43
Muscle Fibers, Fast-Twitch
Calcium
C2C12
Muscle Contraction
Subjects
Details
- ISSN :
- 20734409
- Volume :
- 10
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Cells
- Accession number :
- edsair.doi.dedup.....fe538a4477a6821dcf93e15d3fb2c1f1