title: Fibromodulin and Biglycan Modulate Periodontium through TGFβ/BMP Signaling.
abstract: 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-κB 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 (TGFβ/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 TGFβ/BMP signaling, matrix turnover, and collagen organization.
authors: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, USA le.wang@nih.gov.
authors: L
authors: L
authors: Wang
authors: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, USA.
authors: B L
authors: BL
authors: Foster
authors: National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health (NIH), Bethesda, MD, USA.
authors: V
authors: V
authors: Kram
authors: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, USA State University of Campinas, Piracicaba Dental School, Department of Prosthodontics and Periodontics, Piracicaba, Brazil.
authors: F H
authors: FH
authors: Nociti
authors: Division of Veterinary Resources, Office of Research Services, National Institutes of Health (NIH), Bethesda, MD, USA.
authors: P M
authors: PM
authors: Zerfas
authors: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, USA.
authors: A B
authors: AB
authors: Tran
authors: National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health (NIH), Bethesda, MD, USA.
authors: M F
authors: MF
authors: Young
authors: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, USA.
authors: M J
authors: MJ
authors: Somerman
mesh_terms: D000539:Alveolar Process / Q000473:pathology / Q000502:physiology; D000818:Animals; D058578:Biglycan / Q000502:physiology*; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D016723:Bone Remodeling / Q000502:physiology; D011508:Chondroitin Sulfate Proteoglycans / Q000032:analysis; D003094:Collagen / Q000648:ultrastructure; D058575:Decorin / Q000032:analysis; D016326:Extracellular Matrix Proteins / Q000032:analysis / Q000502:physiology*; D000071235:Fibromodulin; D006706:Homeostasis / Q000502:physiology; D007632:Keratan Sulfate / Q000032:analysis; D000071234:Lumican; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D010010:Osteoclasts / Q000473:pathology; D053495:Osteopontin / Q000032:analysis; D010513:Periodontal Ligament / Q000648:ultrastructure; D010519:Periodontium / Q000502:physiology*; D011509:Proteoglycans / Q000502:physiology*; D053245:RANK Ligand / Q000032:analysis; D015398:Signal Transduction / Q000502:physiology*; D051902:Smad5 Protein / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: C511592:Aspn protein, mouse; C546885:Bgn protein, mouse; D058578:Biglycan; D019485:Bone Morphogenetic Proteins; D011508:Chondroitin Sulfate Proteoglycans; C546879:Dcn protein, mouse; D058575:Decorin; C513308:Dmp1 protein, mouse; D016326:Extracellular Matrix Proteins; C000604332:Fmod protein, mouse; C000604307:Lum protein, mouse; D000071234:Lumican; D011509:Proteoglycans; D053245:RANK Ligand; D051902:Smad5 Protein; C497798:Smad5 protein, mouse; C506896:Spp1 protein, mouse; C505689:Tnfsf11 protein, mouse; D016212:Transforming Growth Factor beta; D053495:Osteopontin; D000071235:Fibromodulin; D003094:Collagen; D007632:Keratan Sulfate
keywords: extracellular matrix; mineralization; periodontal ligament; proteoglycan; signal transduction; tooth root