TY - JOUR
T1 - Effects of the activin A-myostatin-follistatin system on aging bone and muscle progenitor cells
AU - Bowser, Matthew
AU - Herberg, Samuel
AU - Arounleut, Phonepasong
AU - Shi, Xingming
AU - Fulzele, Sadanand
AU - Hill, William D.
AU - Isales, Carlos M.
AU - Hamrick, Mark W.
N1 - Funding Information:
Funding for this research was provided by the Congressionally Directed Medical Research Programs, Department of the Army ( CDMRP093619 ) and the National Institute on Aging ( P01 AG036675 ).
PY - 2013/2
Y1 - 2013/2
N2 - 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.
AB - 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.
KW - Bone marrow stromal cells
KW - Differentiation
KW - Myoblasts
KW - Proliferation
KW - Sarcopenia
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U2 - 10.1016/j.exger.2012.11.004
DO - 10.1016/j.exger.2012.11.004
M3 - Article
C2 - 23178301
AN - SCOPUS:84872827217
SN - 0531-5565
VL - 48
SP - 290
EP - 297
JO - Experimental Gerontology
JF - Experimental Gerontology
IS - 2
ER -