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Publication : Fibromodulin and Biglycan Modulate Periodontium through TGFβ/BMP Signaling.

First Author  Wang L Year  2014
Journal  J Dent Res Volume  93
Issue  8 Pages  780-7
PubMed ID  24966230 Mgi Jnum  J:278906
Mgi Id  MGI:6359250 Doi  10.1177/0022034514541126
Citation  Wang L, et al. (2014) Fibromodulin and Biglycan Modulate Periodontium through TGFbeta/BMP Signaling. J Dent Res 93(8):780-7
abstractText  A full understanding of the key regulators controlling periodontal development and homeostasis is necessary for the design of improved periodontal regenerative therapies. Small leucine-rich proteoglycans (SLRPs) are extracellular matrix molecules suggested to regulate collagen organization and cell signaling. Mice with double-deficiency of 2 SLRPs, fibromodulin and biglycan (dKO), acquire skeletal abnormalities, but their roles in regulating the periodontium remain undefined and were the focus of our studies. Transmission electron microscopy studies showed abnormal collagen fibrils in the periodontal ligament (PDL) and altered remodeling of alveolar bone in dKO mice. Immunohistochemistry (IHC) revealed increased staining of SLRPs (asporin, lumican, and decorin) and dentin matrix protein-1 (DMP1, a mechanosensory/osteocyte marker), while osteoblast markers, bone sialoprotein and osteopontin, remained unchanged. Disruption of homeostasis was further evidenced by increased expression of receptor-activator of nuclear factor-kappaB ligand (RANKL) and elevated numbers of osteoclasts, especially noted around the alveolar bone of molars (buccal side) and incisors. Polymerase chain reaction (PCR) array revealed hyperactive transforming growth factors beta/bone morphogenetic protein (TGFbeta/BMP) signaling in dKO PDL tissues, which was further confirmed by elevated expression of phosphorylated Smad5 (p-Smad5) by IHC in dKO PDL. These studies highlight the importance of SLRPs in maintaining periodontal homeostasis through regulation of TGFbeta/BMP signaling, matrix turnover, and collagen organization.
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