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

• DOI: 10.1210/en.2004-1050
• Publication Date: 2005-01-28T01:25:30Z
• Authors: Feng-Sheng Wang; Chun-Liang Lin; Yeung-Jen Chen; Ching-Jen Wang; Kuender D. Yang; Yu-Ting Huang; Yi-Chih Sun; Hui-Chen Huang
• Keywords: LRP5

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