Enhanced Osteoclastogenesis Causes Osteopenia in Twisted Gastrulation-Deficient Mice Through Increased BMP Signaling

• DOI: 10.1359/jbmr.090507
• Publication Date: 2009-05-06T18:20:32Z
• Authors: Julio E. Sotillo ...; Kim C. Mansky; Eric D. Jensen; Ann E. Carlson; Toni Schwarz; Lan Pham; BreAnne MacKenzie; Hari Prasad; Michael D. Rohrer; Anna Petryk; Rajaram Gopalakri...
• Keywords: Osteopenia; Bone remodeling

Abstract The uncoupling of osteoblastic and osteoclastic activity is central to disorders such as osteoporosis, osteolytic malignancies, periodontitis. Numerous studies have shown explicit functions for bone morphogenetic proteins (BMPs) in skeletogenesis. Their signaling has been various contexts be regulated by extracellular proteins, including Twisted gastrulation (TWSG1). However, experimental paradigms determining the effects BMP regulators on remodeling are limited. In this study, we assessed role TWSG1 postnatal homeostasis. Twsg1-deficient (Twsg1−/−) mice developed osteopenia that could not explained defective osteoblast function, because mineral apposition rate differentiation markers were significantly different compared with wildtype (WT) mice. Instead, discovered a striking enhancement osteoclastogenesis Twsg1−/− mice, leading increased resorption resultant osteopenia. Enhanced was caused cell fusion, differentiation, function osteoclasts. Furthermore, RANKL-mediated phosphorylated Smad1/5/8 levels enhanced when WT osteoclasts treated recombinant BMP2, suggesting direct regulation osteoclast BMPs. Increase detectable Smad 1/5/8 noted from reversed vitro dose-dependent manner exposure Noggin, antagonist, strongly Twsg1 mutants attributable signaling. Thus, present novel previously uncharacterized inhibiting through activity.