BoneKEy Reports | BoneKEy Watch
Biglycan: an important regulator of Wnt signalling in the bone matrix
DOI:10.1038/bonekey.2012.18
Extracellular biglycan, a leucine-rich proteoglycan, appears to interact with the Wnt signalling pathway through its core protein, according to a recent report. In vitro studies revealed that biglycan, the canonical Wnt ligand Wnt3a and the Wnt coreceptor low-density lipoprotein receptor-related protein 6 (LRP6) form a trimeric complex. This enables biglycan to modulate Wnt canonical signalling and to control functional activity in osteoprogenitor cells. Biglycan may impact on both RUNX2-mediated transcription and calcium deposition in bone.
Studies using a bone fracture healing model demonstrated that bone formed by cells deficient in biglycan showed decreased expression of Wnt-induced secreted protein 1, suggesting that biglycan acts to reduce Wnt signalling in vivo.
The authors suggest that biglycan may be a reservoir for Wnt in the bone matrix, and may control the availability of Wnt required to activate the canonical Wnt pathway.
Editor's comment: Canonical Wnt signalling is defective in osteoporosis: this study is the first to present evidence that components of the bone matrix, biglycan in particular, can interact with Wnt-LRP6 signalling in vitro and in vivo. These observations may have important implications for our understanding of the mechanisms that underlie osteoporosis, fracture repair and bone metastasis.
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