Expression and distribution of SIBLING proteins in the predentin/dentin and mandible of hyp mice.
OBJECTIVE
Human X-linked hypophosphatemia (XLH) and its murine homologue, Hyp are caused by inactivating mutations in PHEX gene. The protein encoded by PHEX gene is an endopeptidase whose physiological substrate(s) has not been identified. Dentin matrix protein 1 (DMP1) and dentin sialophosphoprotein (DSPP), two members of the Small Integrin-Binding LIgand, N-linked Glycoprotein (SIBLING) family are proteolytically processed. It has been speculated that PHEX endopeptidase may be responsible for the proteolytic cleavage of DMP1 and DSPP. To test this hypothesis and to analyse the distribution of SIBLING proteins in the predentin/dentin complex and mandible of Hyp mice, we compared the expression of four SIBLING proteins, DMP1, DSPP, bone sialoprotein (BSP) and osteopontin (OPN) between Hyp and wild-type mice.


METHODS
These SIBLING proteins were analysed by protein chemistry and immunohistochemistry.


RESULTS
(1) Dentin matrix protein 1 and DSPP fragments are present in the extracts of Hyp predentin/dentin and bone; (2) the level of DMP1 proteoglycan form, BSP and OPN is elevated in the Hyp bone.


CONCLUSIONS
The PHEX protein is not the enzyme responsible for the proteolytic processing of DMP1 and DSPP. The altered distribution of SIBLING proteins may be involved in the pathogenesis of bone and dentin defects in Hyp and XLH.
Zhang
B
B
Department of Oral and Maxillofacial Surgery, 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China. zhangbinhmu@126.com
Sun
Y
Y
Chen
L
L
Guan
C
C
Guo
L
L
Qin
C
C
D000818:Animals; D015153:Blotting, Western; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D004396:Coloring Agents; D003804:Dentin / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D016326:Extracellular Matrix Proteins / Q000032:analysis*; D053098:Familial Hypophosphatemic Rickets / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005456:Fluorescent Dyes; D040181:Genetic Diseases, X-Linked; D007150:Immunohistochemistry; D058574:Integrin-Binding Sialoprotein; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D053495:Osteopontin / Q000032:analysis*; D053402:PHEX Phosphate Regulating Neutral Endopeptidase / Q000235:genetics; D010750:Phosphoproteins / Q000032:analysis*; D012795:Sialoglycoproteins / Q000032:analysis*; D000099311:Dentin Sialophosphoprotein
D004396:Coloring Agents; D016326:Extracellular Matrix Proteins; D005456:Fluorescent Dyes; D058574:Integrin-Binding Sialoprotein; D053495:Osteopontin; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; D010750:Phosphoproteins; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein; C513308:Dmp1 protein, mouse; C546871:IBSP protein, human; C546872:Ibsp protein, mouse; C506896:Spp1 protein, mouse; C506232:Phex protein, mouse