Skeletal muscle secreted factors prevent glucocorticoid-induced osteocyte apoptosis through activation of β-catenin

K. Jähn, N. Lara-Castillo, L. Brotto, C. L. Mo, M. L. Johnson, M. Brotto, Lynda Bonewald

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

It is a widely held belief that the sole effect of muscle on bone is through mechanical loading. However, as the two tissues are intimately associated, we hypothesized that muscle myokines may have positive effects on bone. We found that factors produced by muscle will protect osteocytes from undergoing cell death induced by dexamethasone (dex), a glucocorticoid known to induce osteocyte apoptosis thereby compromising their capacity to regulate bone remodeling. Both the trypan blue exclusion assay for cell death and nuclear fragmentation assay for apoptosis were used. MLO-Y4 osteocytes, primary osteocytes, and MC3T3 osteoblastic cells were protected against dex-induced apoptosis by C2C12 myotube conditioned media (MT-CM) or by CM from ex vivo electrically stimulated, intact extensor digitorum longus (EDL) or soleus muscle derived from 4 month-old mice. C2C12 MT-CM, but not undifferentiated myoblast CM prevented dex-induced cell apoptosis and was potent down to 0.1 % CM. The CM from EDL muscle electrically stimulated tetanically at 80 Hz was more potent (10 fold) in prevention of dex-induced osteocyte death than CM from soleus muscle stimulated at the same frequency or CM from EDL stimulated at 1 Hz. This suggests that electrical stimulation increases production of factors that preserve osteocyte viability and that type II fibers are greater producers than type I fibers. The muscle factor(s) appears to protect osteocytes from cell death through activation of the Wnt/β-catenin pathway, as MT-CM induces β-catenin nuclear translocation and β-catenin siRNA abrogated the positive effects of MT-CM on dex-induced apoptosis. We conclude that muscle cells naturally secrete factor(s) that preserve osteocyte viability.

Original languageEnglish (US)
Pages (from-to)197-210
Number of pages14
JournalEuropean Cells and Materials
Volume24
StatePublished - Jul 2012
Externally publishedYes

Fingerprint

Osteocytes
Catenins
Cell death
Glucocorticoids
Muscle
Skeletal Muscle
Chemical activation
Apoptosis
Dexamethasone
Skeletal Muscle Fibers
Conditioned Culture Medium
Muscles
Bone
Cell Death
Assays
Bone and Bones
Wnt Signaling Pathway
Trypan Blue
Fibers
Bone Remodeling

Keywords

  • β-catenin
  • Aging
  • Apoptosis
  • Bone
  • Glucocorticoid
  • Osteocytes

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Bioengineering
  • Biomedical Engineering
  • Biomaterials
  • Medicine(all)

Cite this

Skeletal muscle secreted factors prevent glucocorticoid-induced osteocyte apoptosis through activation of β-catenin. / Jähn, K.; Lara-Castillo, N.; Brotto, L.; Mo, C. L.; Johnson, M. L.; Brotto, M.; Bonewald, Lynda.

In: European Cells and Materials, Vol. 24, 07.2012, p. 197-210.

Research output: Contribution to journalArticle

Jähn, K. ; Lara-Castillo, N. ; Brotto, L. ; Mo, C. L. ; Johnson, M. L. ; Brotto, M. ; Bonewald, Lynda. / Skeletal muscle secreted factors prevent glucocorticoid-induced osteocyte apoptosis through activation of β-catenin. In: European Cells and Materials. 2012 ; Vol. 24. pp. 197-210.
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