Endocrinology, Vol 137, 4250-4259, Copyright © 1996 by Endocrine Society

ARTICLES

Follistatin and activin in bone: expression and localization during endochondral bone development

M Funaba, K Ogawa, T Murata, H Fujimura, E Murata, M Abe, M Takahashi and K Torii
Torii Nutrient-Stasis Project, ERATO, R&D Corp. of Japan, Yokohama, Japan.

The involvement of activin and follistatin, an activin-binding protein, in endochondral bone development was examined by sc implantation of demineralized bone matrix in rats. Immunoreactive follistatin was localized in proliferating chondrocytes and round osteoblasts, whereas it was not detected in hypertrophic chondrocytes and osteoblasts surrounding bone marrow. Western blot analysis also revealed that immunoreactive follistatin was higher during the initial stages of chondrogenesis (day 5) and osteogenesis (days 11 and 14) and lower during the conversion from cartilage to bone (day 9). These results suggest that follistatin is produced by proliferating cells, and the expression decreases with differentiation of the cells. Implants injected with follistatin on days 9 and 10 contained lower calcium levels on day 14 than those injected with rat albumin. Furthermore, the follistatin-injected implants were still mainly composed of cartilage, suggesting that the disappearance of follistatin is necessary for the conversion of cartilage to bone. In contrast, immunoreactive activin beta A (55-60 kDa) was continuously detected in implants on days 7-14. The content of C propeptide of type II procollagen was increased and cartilageous area was enlarged on day 7 by activin A injections on days 5 and 6, suggesting a chondrogenic effect of activin in the initial stage of cartilage formation. These results indicate that proliferating chondrocytes and round osteoblasts produce follistatin, and that the activity of activin is regulated by changes in the expression of follistatin at the stages of chondrogenesis and transition from cartilage to bone.

This article has been cited by other articles:

				D. S. Perrien, N. S. Akel, P. K. Edwards, A. A. Carver, M. S. Bendre, F. L. Swain, R. A. Skinner, W. R. Hogue, K. M. Nicks, T. M. Pierson, et al. Inhibin A Is an Endocrine Stimulator of Bone Mass and Strength Endocrinology, April 1, 2007; 148(4): 1654 - 1665. [Abstract] [Full Text] [PDF]

				D. S. Perrien, S. J. Achenbach, S. E. Bledsoe, B. Walser, L. J. Suva, S. Khosla, and D. Gaddy Bone Turnover across the Menopause Transition: Correlations with Inhibins and Follicle-Stimulating Hormone J. Clin. Endocrinol. Metab., May 1, 2006; 91(5): 1848 - 1854. [Abstract] [Full Text] [PDF]

				C. J. Jorgez, M. Klysik, S. P. Jamin, R. R. Behringer, and M. M. Matzuk Granulosa Cell-Specific Inactivation of Follistatin Causes Female Fertility Defects Mol. Endocrinol., April 1, 2004; 18(4): 953 - 967. [Abstract] [Full Text] [PDF]

				E. Canalis, A. N. Economides, and E. Gazzerro Bone Morphogenetic Proteins, Their Antagonists, and the Skeleton Endocr. Rev., April 1, 2003; 24(2): 218 - 235. [Abstract] [Full Text] [PDF]

				C. Welt, Y. Sidis, H. Keutmann, and A. Schneyer Activins, Inhibins, and Follistatins: From Endocrinology to Signaling. A Paradigm for the New Millennium Experimental Biology and Medicine, October 1, 2002; 227(9): 724 - 752. [Abstract] [Full Text] [PDF]

				Y. Sidis, D. V. Tortoriello, W. E. Holmes, Y. Pan, H. T. Keutmann, and A. L. Schneyer Follistatin-Related Protein and Follistatin Differentially Neutralize Endogenous vs. Exogenous Activin Endocrinology, May 1, 2002; 143(5): 1613 - 1624. [Abstract] [Full Text] [PDF]

				D. Gaddy-Kurten, J. K. Coker, E. Abe, R. L. Jilka, and S. C. Manolagas Inhibin Suppresses and Activin Stimulates Osteoblastogenesis and Osteoclastogenesis in Murine Bone Marrow Cultures Endocrinology, January 1, 2002; 143(1): 74 - 83. [Abstract] [Full Text] [PDF]

				E. Y. Wang, L. B. Draper, E. Lee, A. Polak, P. Sluss, J. Weiss, and T. K. Woodruff Identification of Naturally Occurring Follistatin Complexes in Human Biological Fluids Biol Reprod, January 1, 1999; 60(1): 8 - 13. [Abstract] [Full Text]