Effects of the activin A-myostatin-follistatin system on aging bone and muscle progenitor cells

Matthew Bowser, Samuel Herberg, Phonepasong Arounleut, Xing Ming Shi, Sadanand T Fulzele, William D Hill, Carlos M Isales, Mark W Hamrick

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

The activin A-myostatin-follistatin system is thought to play an important role in the regulation of muscle and bone mass throughout growth, development, and aging; however, the effects of these ligands on progenitor cell proliferation and differentiation in muscle and bone are not well understood. In addition, age-associated changes in the relative expression of these factors in musculoskeletal tissues have not been described. We therefore examined changes in protein levels of activin A, follistatin, and myostatin (GDF-8) in both muscle and bone with age in C57BL6 mice using ELISA. We then investigated the effects of activin A, myostatin and follistatin on the proliferation and differentiation of primary myoblasts and mouse bone marrow stromal cells (BMSCs) in vitro. Myostatin levels and the myostatin:follistatin ratio increased with age in the primarily slow-twitch mouse soleus muscle, whereas the pattern was reversed with age in the fast-twitch extensor digitorum longus muscle. Myostatin levels and the myostatin:follistatin ratio increased significantly (+. 75%) in mouse bone marrow with age, as did activin A levels (+. 17%). Follistatin increased the proliferation of primary myoblasts from both young and aged mice, whereas myostatin increased proliferation of younger myoblasts but decreased proliferation of older myoblasts. Myostatin reduced proliferation of both young and aged BMSCs in a dose-dependent fashion, and activin A increased mineralization in both young and aged BMSCs. Together these data suggest that aging in mice is accompanied by changes in the expression of activin A and myostatin, as well as changes in the response of bone and muscle progenitor cells to these factors. Myostatin appears to play a particularly important role in the impaired proliferative capacity of muscle and bone progenitor cells from aged mice.

Original languageEnglish (US)
Pages (from-to)290-297
Number of pages8
JournalExperimental Gerontology
Volume48
Issue number2
DOIs
StatePublished - Feb 1 2013

Fingerprint

Myostatin
Follistatin
Muscle Cells
Muscle
Bone
Stem Cells
Aging of materials
Bone and Bones
Myoblasts
Muscles
Mesenchymal Stromal Cells
activin A
Cell proliferation
Growth and Development
Cell Differentiation

Keywords

  • Bone marrow stromal cells
  • Differentiation
  • Myoblasts
  • Proliferation
  • Sarcopenia

ASJC Scopus subject areas

  • Aging
  • Biochemistry
  • Cell Biology
  • Endocrinology
  • Genetics
  • Molecular Biology

Cite this

Effects of the activin A-myostatin-follistatin system on aging bone and muscle progenitor cells. / Bowser, Matthew; Herberg, Samuel; Arounleut, Phonepasong; Shi, Xing Ming; Fulzele, Sadanand T; Hill, William D; Isales, Carlos M; Hamrick, Mark W.

In: Experimental Gerontology, Vol. 48, No. 2, 01.02.2013, p. 290-297.

Research output: Contribution to journalArticle

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