The Study Of Roles Of Dentin Sialophosphoprotein (DSPP) In The Postnatal Development And Maintenance Of Mouse Mandibular Condylar Cartilage

Dentin sialophosphoprotein (DSPP) belongs to SIBLING protein family, it is a largerprecursor protein and can be proteolyticly processed into two functional fragments: DSP andDPP. Previously, it was thought to be dentin speciifc. In physiological conditions DSPP ispresent in the extracellular matrix (ECM) of dentin in the form of DSP and DPP fragments,which paly crucial roles in different ways. It has been demonstrated that the proteolyticprocessing of DSPP in the ECM of dentin is an essential activation step for its biologicalfunction in biomineralization, if the process was blocked，the dentin formation will beseverely affected.Nowadays, in the exception of in dentin, DSPP was found to be expressed in some otherhard tissues such as bone，cementum, and a bunch of non-mineralized tissues: salivaryglands, cartilage, liver, lung, kidney, and brain et al. However, the role DSPP plays in thesetissue was unclear.In distinct cartilage tissues or among cartilages and hard tissues, DSPP differs fromeach other in some marked ways： DSPP in the ECM of dentin and femoral head is primarilypresent as processed DSP and DPP fragments, originating from the NH2-terminal andCOOH-terminal regions of the DSPP amino acid sequence, respectively, while in mandibularcondylar cartilage the majority of DSPP in the condylar cartilage appears uncleaved, i.e.existing as the intact, full-length form; Additionally, Western immunoblotting by theanti-DSP antibody showed that the migration rate of DSP extracted from the femoral headcartilage was faster than that from rat incisor dentin, indicating that DSP in the cartilage may be devoid of any carbohydrate substituents; furthermore, although the level of DSPPexpression in the cartilage is lower than that in dentin, it appears much higher in the cartilagethan in the long bone. These ifndings suggest that the biological role of DSPP in the condylarcartilage may differ from that in dentin and bone. Further studies are warranted to analyzethe roles of DSPP in the cartilage tissues.Dspp null mice develop tooth defects with enlarged pulp chambers, increased width ofpredentin zone，hypomineralization, and pulp explosure. As DSPP is expressed at a very lowlevel in the long bone，its disruption in mice resulted in modest but signiifcant changes in thematerial properties of long bone at certain time points. While the levels of DSPP expressionin cartilage are higher than that in the long bone，there has no reports regarding thephenotypic alterations in the cartilage of Dspp null mice.The mandibular cartilage is termed as secondary cartilage, it differs from primarycartilage in its unique embryonic origin，oncogenic development, post-natal growth modeand histological structure features. It has raised considerable concern cause of its crucial rolein the development and function of the mandible. Here, in this investigation the Dspp nullmice were used as an animal model，compared with the WT mice，the mandibular condyleand mandibular condylar cartilage was observed and examined, and the roles of DSPP inmouse mandibular condylar cartilage development and maintenance was preliminarilystudied.To analyze such roles，we examined Dspp null mice compared with wild type (WT)mice to assess the consequences of Dspp deletion on the morphology and structure of themandibular condylar cartilage. Plain x-ray and jaCT data showed that at the ages of3and6months the mandibular condyle is thinner in Dspp null mice than WT mice. The condylesurface of Dspp null mice became more flattened in comparison with the WT mice of same age. At postnatal2months, no signiifcant differences between the two groups could bedistinguished by plain x-ray examination. The histopathological analysis showed that DSPPis expressed in the prechondroblastic, chondroblastic, hypertrophic layers of the mandibularcondylar cartilage. Dspp null mice exhibited decreases of mandibular condylar cartilage withreduced formation of articular and prechondroblastic layers in which the progenitor cellproliferation in the mandibular condylar cartilage was distinctly affected. Additionally, theexpression of extracellular matrix molecules including biglycan，collagen II，IX，X wereremarkably altered.In conclusion, the loss of DSPP alters the development of different layers of the MCC.During the development of the MCC, DSPP may be involved in the proliferation ofprogenitor cells and the regulation of ECM molecule synthesis or assembly in the cartilage.The ifndings in this study indicate that DSPP is essential for maintaining a healthy condylarcartilage in the mouse mandible.