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Effects of the activin A-myostatin-follistatin system on aging bone and muscle progenitor cells.
Exp Gerontol. 2013 Feb; 48(2):290-7.EG

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.

Authors+Show Affiliations

Georgia Health Sciences University, Augusta, GA 30912, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

23178301

Citation

Bowser, Matthew, et al. "Effects of the Activin A-myostatin-follistatin System On Aging Bone and Muscle Progenitor Cells." Experimental Gerontology, vol. 48, no. 2, 2013, pp. 290-7.
Bowser M, Herberg S, Arounleut P, et al. Effects of the activin A-myostatin-follistatin system on aging bone and muscle progenitor cells. Exp Gerontol. 2013;48(2):290-7.
Bowser, M., Herberg, S., Arounleut, P., Shi, X., Fulzele, S., Hill, W. D., Isales, C. M., & Hamrick, M. W. (2013). Effects of the activin A-myostatin-follistatin system on aging bone and muscle progenitor cells. Experimental Gerontology, 48(2), 290-7. https://doi.org/10.1016/j.exger.2012.11.004
Bowser M, et al. Effects of the Activin A-myostatin-follistatin System On Aging Bone and Muscle Progenitor Cells. Exp Gerontol. 2013;48(2):290-7. PubMed PMID: 23178301.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2012/11/21/ PY - 2012/09/25/received PY - 2012/11/08/revised PY - 2012/11/11/accepted PY - 2012/11/27/entrez PY - 2012/11/28/pubmed PY - 2013/7/9/medline SP - 290 EP - 7 JF - Experimental gerontology JO - Exp. Gerontol. VL - 48 IS - 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. SN - 1873-6815 UR - https://www.unboundmedicine.com/medline/citation/23178301/Effects_of_the_activin_A_myostatin_follistatin_system_on_aging_bone_and_muscle_progenitor_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0531-5565(12)00301-4 DB - PRIME DP - Unbound Medicine ER -