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Myokines (muscle-derived cytokines and chemokines) including ciliary neurotrophic factor (CNTF) inhibit osteoblast differentiation
- Source :
- Bone. 64
- Publication Year :
- 2013
-
Abstract
- Muscle and bone are intimately linked by bi-directional signals regulating both muscle and bone cell gene expression and proliferation. It is generally accepted that muscle cells secrete factors (myokines) that influence adjacent bone cells, but these myokines are yet to be identified. We have previously shown that osteocyte-specific deletion of the co-receptor subunit utilized by IL-6 family cytokines, glycoprotein 130 (gp130), resulted in impaired bone formation in the trabecular bone, but enhanced periosteal expansion, suggesting a gp130-dependent periosteum-specific inhibition of osteoblast function, potentially induced by the local muscle fibres. We report here that differentiated primary calvarial osteoblasts cultured in myotube-conditioned media (CM) from myogenic C2C12 cells show reduced mRNA levels of genes associated with osteoblast differentiation. Alkaline phosphatase protein activity and all mRNA markers of osteoblast differentiation in the tested panel (runx2, osterix, alkaline phosphatase, parathyroid hormone (PTH) receptor, osteoprotegerin, osteocalcin, sclerostin) were reduced following culture with myotube CM. The exception was RANKL, which was significantly elevated in differentiated primary osteoblast cultures expressing osteocytic genes. A cytokine array of the C2C12 myotube-conditioned media identified TIMP-1 and MCP-1 as the most abundant myokines, but treatment with recombinant TIMP-1 or MCP-1 did not inhibit osteoblast gene expression. Rather, the IL-6 family cytokine ciliary neurotrophic factor (CNTF), which we found abundantly expressed by mouse muscle at the transcript and protein level, reduced osteoblast gene expression, although not to the same extent as the myotube-conditioned media. These data indicate that muscle cells secrete abundant TIMP-1, MCP-1, and CNTF, and that of these, only CNTF has the ability to suppress osteoblast function and gene expression in a similar manner to myotube-conditioned medium. This suggests that CNTF is an inhibitory myokine for osteoblasts.
- Subjects :
- musculoskeletal diseases
medicine.medical_specialty
Histology
Physiology
Endocrinology, Diabetes and Metabolism
Gene Expression
Biology
Ciliary neurotrophic factor
Cell Line
Mice
Osteoprotegerin
Internal medicine
Bone cell
medicine
Animals
Ciliary Neurotrophic Factor
Receptor, Ciliary Neurotrophic Factor
Osteoblasts
RANK Ligand
Skeletal muscle
Osteoblast
Cell Differentiation
Glycoprotein 130
RUNX2
Mice, Inbred C57BL
Endocrinology
medicine.anatomical_structure
RANKL
Culture Media, Conditioned
biology.protein
Cytokines
Chemokines
Subjects
Details
- ISSN :
- 18732763
- Volume :
- 64
- Database :
- OpenAIRE
- Journal :
- Bone
- Accession number :
- edsair.doi.dedup.....0fbd164c39b3582757ebc88d69bc73d1