This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: 146/5/2415    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, F.-S. Articles by Huang, H.-C. Search for Related Content PubMed PubMed Citation Articles by Wang, F.-S. Articles by Huang, H.-C.

Secreted Frizzled-Related Protein 1 Modulates Glucocorticoid Attenuation of Osteogenic Activities and Bone Mass

Departments of Medical Research (F.-S.W., K.D.Y., Y.-T.H., Y.-C.S., H.-C.H.), and Orthopedic Surgery (C.-J.W.), Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan; Department of Nephrology (C.-L.L.), Chayi Chang Gung Memorial Hospital, Chayi 613, Taiwan; and Department of Orthopedic Surgery (Y.-J.C.) Chang Gung University, Linko 244, Taiwan

Address all correspondence and requests for reprints to: Kuender D. Yang, Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao Sung, Kaohsiung 833, Taiwan. E-mail: wangfs{at}ms33.hinet.net.

Prolonged glucocorticoid treatment is known to cause osteoporosis or aseptic necrosis. Secreted frizzled-related proteins 1 (SFRP1) and low-density lipoprotein-related protein 5 (LRP5), a Wnt protein antagonist and a coreceptor, have been found to regulate skeletogenesis. Whereas recent studies have reported that excess glucocorticoid promotes bone loss, the biological role of SFRP1 and LRP5 in regulating glucocorticoid attenuation of bone formation is not fully understood. We showed that a supraphysiological level of glucocorticoid enhanced SFRP1 but not LRP5 expression of primary mesenchymal cell cultures in vitro and osteoblasts at metaphyseal trabecular endosteum and chondrocytes at calcified cartilage in vivo. Glucocorticoid augmentation of SFRP1 expression was transcriptionally mediated. The inhibitory action of glucocorticoid on osteogenic differentiation appeared to be regulated by SFRP1 mediation of ß-catenin destabilization because knocking down SFRP1 by RNA interference abrogated the supraphysiological level of glucocorticoid attenuation of osteogenesis. Recombinant human SFRP1 reduced the promoting effect of physiological level of glucocorticoid on cytosolic ß-catenin accumulation, runt-related transcription factor-2 activation, and osteogenic activities. Glucocorticoid and recombinant human SFRP1 significantly increased osteochondral cell apoptosis associated with reduced mineral density, biomechanical properties, trabecular bone volume, and midshaft cortical bone areas in rat femurs. These findings suggest that SFRP1 modulates glucocorticoid-induced bone loss. Regulation of Wnt/SFRP signal transduction can be used in the future as an alternative strategy for the prevention of glucocorticoid-induced osteoporosis.

This article has been cited by other articles:

				M. Nagayama, M. Iwamoto, A. Hargett, N. Kamiya, Y. Tamamura, B. Young, T. Morrison, H. Takeuchi, M. Pacifici, M. Enomoto-Iwamoto, et al. Wnt/{beta}-catenin Signaling Regulates Cranial Base Development and Growth J. Dent. Res., March 1, 2008; 87(3): 244 - 249. [Abstract] [Full Text] [PDF]

				P. V. Bodine Wnt Signaling in Bone IBMS BoneKEy, March 1, 2007; 4(3): 108 - 123. [Abstract] [Full Text] [PDF]

				V. Deregowski, E. Gazzerro, L. Priest, S. Rydziel, and E. Canalis Notch 1 Overexpression Inhibits Osteoblastogenesis by Suppressing Wnt/beta-Catenin but Not Bone Morphogenetic Protein Signaling J. Biol. Chem., March 10, 2006; 281(10): 6203 - 6210. [Abstract] [Full Text] [PDF]