scholarly journals Dentin Sialophosphoprotein Deletion Leads to Femoral Head Cartilage Attenuation and Subchondral Bone Ill-mineralization

2020 ◽  
Vol 68 (10) ◽  
pp. 703-718
Author(s):  
Qilin Liu ◽  
Ning Ma ◽  
Qinglin Zhu ◽  
Xiaoqin Duan ◽  
Haibo Shi ◽  
...  
Keyword(s):  
Femoral Head ◽  
Subchondral Bone ◽  
Matrix Protein ◽  
Bone Mineralization ◽  
Tartrate Resistant Acid Phosphatase ◽  
Cartilage Growth ◽  
Dentin Sialophosphoprotein ◽  
Dentin Matrix Protein ◽  
Femoral Head Cartilage ◽  
Cartilage Cells

Dentin sialophosphoprotein (DSPP), which expresses and synthesizes in odontoblasts of dental pulp, is a critical protein for normal teeth mineralization. Originally, DSPP was identified as a dentin-specific protein. In 2010, DSPP was also found in femoral head cartilage, and it is still unclear what roles DSPP play in femoral head cartilage formation, growth, and maintenance. To reveal biological functions of DSPP in the femoral head cartilage, we examined Dspp null mice compared with wild-type (WT) mice to observe DSPP expression as well as localization in WT mice and to uncover differences of femoral head cartilage, bone morphology, and structure between these two kinds of mice. Expression data demonstrated that DSPP had heterogeneous fragments, expressed in each layer of femoral head cartilage and subchondral bone of WT mice. Dspp null mice exhibited a significant reduction in the thickness of femoral head cartilage, with decreases in the amount of proliferating cartilage cells and increases in apoptotic cells. In addition, the subchondral bone mineralization decreased, and the expressions of vessel markers (vascular endothelial growth factor [VEGF] and CD31), osteoblast markers (Osterix and dentin matrix protein 1 [DMP1]), osteocyte marker (sclerostin [SOST]), and osteoclast marker (tartrate-resistant acid phosphatase [TRAP]) were remarkably altered. These indicate that DSPP deletion can affect the proliferation of cartilage cells in the femoral head cartilage and endochondral ossification in subchondral bone. Our data clearly demonstrate that DSPP plays essential roles in the femoral head cartilage growth and maintenance and subchondral biomineralization.

scholarly journals Mechanical forces switch blood vessel subtypes to arrest adolescent bone growth

2021 ◽  
Author(s):  
Max Löhning ◽  
Maria Dzamukova ◽  
Tobias Brunner ◽  
Jadwiga Miotla-Zarebska ◽  
Frederik Heinrich ◽  
...  
Keyword(s):  
Blood Vessel ◽  
Matrix Protein ◽  
Bone Growth ◽  
Bone Mineralization ◽  
Extracellular Matrix Protein ◽  
Mechanical Forces ◽  
Dentin Matrix Protein ◽  
Enhanced Production ◽  
Key Factor ◽  
Endothelial Growth Factor

Abstract Bone growth requires a specialised, highly angiogenic blood vessel subtype, so-called type H vessels1,2, which pave the way for osteoblasts surrounding these vessels3. At the end of adolescence, type H endothelial cells differentiate into quiescent type L endothelium lacking the capacity to promote bone growth. Until now, the signals that switch off type H vessel identity and thus arrest adolescent bone growth have remained ill defined. Here we show that mechanical forces, associated with increased body weight at the end of adolescence, trigger the mechanoreceptor PIEZO1 and thereby mediate enhanced production of the kinase FAM20C in osteoblasts. FAM20C phosphorylates dentin matrix protein 1 (DMP1)4, previously identified as a key factor in bone mineralization5. This phosphorylation elicits a burst in DMP1 secretion from osteoblasts. Extracellular DMP1 inhibits vascular endothelial growth factor (VEGF) signalling by preventing VEGFR2 phosphorylation and VEGFR3 expression on the tip cells of type H endothelium. DMP1-mediated VEGF inhibition transforms bone growth-promoting type H vessels into quiescent type L vasculature to arrest bone growth and enhance bone mineralization. This molecular mechanism links mechanical forces and the termination of bone growth via accumulation of an extracellular matrix protein and its regulation of vascular subtypes. It suggests new options for the treatment of diseases characterised by inappropriate turnover or invasion of bone such as osteoarthritis, osteoporosis and osteosarcoma.

scholarly journals A NovelPHEXMutation in Japanese Patients with X-Linked Hypophosphatemic Rickets

2015 ◽  
Vol 2015 ◽  
pp. 1-5
Author(s):  
Tetsuya Kawahara ◽  
Hiromi Watanabe ◽  
Risa Omae ◽  
Toshiyuki Yamamoto ◽  
Tetsuya Inazu
Keyword(s):  
Female Patient ◽  
Matrix Protein ◽  
Bone Mineralization ◽  
Fibroblast Growth Factor 23 ◽  
Japanese Patients ◽  
Hypophosphatemic Rickets ◽  
Gene Encoding ◽  
Vitamin D Metabolism ◽  
Dentin Matrix Protein ◽  
Disease Associated Genes

X-linked hypophosphatemic rickets (XLH) is a dominant inherited disorder characterized by renal phosphate wasting, aberrant vitamin D metabolism, and abnormal bone mineralization. Inactivating mutations in the gene encoding phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) have been found to be associated with XLH. Here, we report a 16-year-old female patient affected by hypophosphatemic rickets. We evaluated her serum fibroblast growth factor 23 (FGF23) levels and conducted sequence analysis of the disease-associated genes of FGF23-related hypophosphatemic rickets:PHEX,FGF23, dentin matrix protein 1, and ectonucleotide pyrophosphatase/phosphodiesterase 1. She was diagnosed with XLH based on her clinical features and family history. Additionally, we observed elevated FGF23 levels and a novelPHEXexon 9 mutation (c.947G>T; p.Gly316Val) inherited from her father. Although bioinformatics showed that the mutation was neutral, Gly316 is perfectly conserved among humans, mice, and rats, and there were no mutations in other FGF23-related rickets genes, suggesting thatin silicoanalysis is limited in determining mutation pathogenicity. In summary, we present a female patient and her father with XLH harboring a novelPHEXmutation that appears to be causative of disease. Measurement of FGF23 for hypophosphatemic patients is therefore useful for the diagnosis of FGF23-dependent hypophosphatemia.

scholarly journals BMP1 and TLL1 Are Required for Maintaining Periodontal Homeostasis

2017 ◽  
Vol 96 (5) ◽  
pp. 578-585 ◽  
Author(s):  
J. Wang ◽  
D. Massoudi ◽  
Y. Ren ◽  
A.M. Muir ◽  
S.E. Harris ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Matrix Protein ◽  
Type I Collagen ◽  
Alveolar Bone ◽  
Significant Loss ◽  
Tartrate Resistant Acid Phosphatase ◽  
Type I ◽  
Dentin Matrix Protein ◽  
Morphogenetic Protein ◽  
Periodontal Breakdown

Mutations in bone morphogenetic protein 1 (BMP1) in humans or deletion of BMP1 and related protease tolloid like 1 (TLL1) in mice lead to osteogenesis imperfecta (OI). Here, we show progressive periodontal defects in mice in which both BMP1 and TLL1 have been conditionally ablated, including malformed periodontal ligament (PDL) (recently shown to play key roles in normal alveolar bone formation), significant loss in alveolar bone mass ( P < 0.01), and a sharp reduction in cellular cementum. Molecular mechanism studies revealed a dramatic increase in the uncleaved precursor of type I collagen (procollagen I) and a reduction in dentin matrix protein 1 (DMP1), which is partially responsible for defects in extracellular matrix (ECM) formation and mineralization. We also showed a marked increase in the expression of matrix metallopeptidase 13 (MMP13) and tartrate-resistant acid phosphatase (TRAP), leading to an acceleration in periodontal breakdown. Finally, we demonstrated that systemic application of antibiotics significantly improved the alveolar bone and PDL damage of the knockdown phenotype, which are thus shown to be partially secondary to pathogen-induced inflammation. Together, identification of the novel roles of BMP1 and TLL1 in maintaining homeostasis of periodontal formation, partly via biosynthetic processing of procollagen I and DMP1, provides novel insights into key contributions of the extracellular matrix environment to periodontal homeostasis and contributes toward understanding of the pathology of periodontitis.

scholarly journals Dentin Matrix Protein 1 Regulates Dentin Sialophosphoprotein Gene Transcription during Early Odontoblast Differentiation

2006 ◽  
Vol 281 (28) ◽  
pp. 19064-19071 ◽  
Author(s):  
Karthikeyan Narayanan ◽  
Sivakumar Gajjeraman ◽  
Amsaveni Ramachandran ◽  
Jianjun Hao ◽  
Anne George
Keyword(s):  
Gene Transcription ◽  
Matrix Protein ◽  
Dentin Matrix Protein 1 ◽  
Dentin Sialophosphoprotein ◽  
Dentin Matrix Protein ◽  
Odontoblast Differentiation ◽  
Dentin Matrix

scholarly journals Histochemical Examination on Periodontal Tissues of Klotho-Deficient Mice Fed With Phosphate-Insufficient Diet

2017 ◽  
Vol 65 (4) ◽  
pp. 207-221 ◽  
Author(s):  
Kumiko Hikone ◽  
Tomoka Hasegawa ◽  
Erika Tsuchiya ◽  
Hiromi Hongo ◽  
Muneteru Sasaki ◽  
...  
Keyword(s):  
Matrix Protein ◽  
Fibroblast Growth Factor 23 ◽  
Elevated Serum ◽  
Normal Diet ◽  
Tartrate Resistant Acid Phosphatase ◽  
Dentin Matrix Protein ◽  
Periodontal Tissues ◽  
Dentin Matrix ◽  
Deficient Mice ◽  
Interalveolar Septum

To elucidate which of elevated serum concentration of inorganic phosphate (Pi) or disrupted signaling linked to αklotho/fibroblast growth factor 23 (FGF23) is a predominant regulator for senescence-related degeneration seen in αKlotho-deficient mice, we have examined histological alteration of the periodontal tissues in the mandibular interalveolar septum of αKlotho-deficient mice fed with Pi-insufficient diet. We prepared six groups of mice: wild-type, kl/kl, and αKlotho−/− mice with normal diet or low-Pi diet. As a consequence, kl/klnorPi and αKlotho−/−norPi mice showed the same abnormalities in periodontal tissues: intensely stained areas with hematoxylin in the interalveolar septum, dispersed localization of alkaline phosphatase–positive osteoblasts and tartrate-resistant acid phosphatase–reactive osteoclasts, and accumulation of dentin matrix protein 1 in the osteocytic lacunae. Although kl/kllowPi mice improved these histological abnormalities, αKlotho−/− lowPi mice failed to normalize those. Gene expression of αKlotho was shown to be increased in kl/kl lowPi specimens. It seems likely that histological abnormalities of kl/kl mice have been improved by the rescued expression of αKlotho, rather than low concentration of serum Pi. Thus, the histological malformation in periodontal tissues in αKlotho-deficient mice appears to be due to not only increased concentration of Pi but also disrupted αklotho/FGF23 signaling.

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