73 Studies of Dmp1-null Condyle Defect

Thursday, March 22, 2012: 8 a.m. - 9:30 a.m.
Presentation Type: Oral Session
T. KOREN1, Q. ZHANG2, S. LIN1, K. YAN1, Y. LIU1, C. QIN1, and J.Q. FENG1, 1Department of Biomedical Sciences, Baylor College of Dentistry, Dallas, TX, 2Deptartment of Endodontics, Wuhan University, Wuhan, China
Objective: Previously we reported that DMP1 (Dentin matrix protein 1) mutation in humans or Dmp1-null mice display hypophosphatemic rickets, including both bone and tooth phenotype. DMP1 was also found in articular cartilage. The goal of this research was to study Dmp1 expression patterns during condyle development, to characterize Dmp1-null condyle phenotype, to address if DMP1 has a direct role in condyle cartilage.

Method: 1) Dmp1-lacZ knock-in (i.e., conventional KO) mice, where the endogenous Dmp1 is replaced by lacZ for tracing Dmp1 expression and deletion phenotype; 2) Dmp1-lacZ knock-in mice were treated with high Pi diet or FGF23 neutralizing antibodies starting from day 6 to 28; 3) Dmp1 loxP mice were crossed to the Col X-Cre mice for tissue specific deletion of Dmp1 (cKO) in cartilage only; and 4) combined approaches of x-ray, micro-CT, and histology methods were used to characterize the mandibular condyle phenotypes.

Result: 1) X-gal staining assay showed that Dmp1-lacZ and Col 10-Cre were mainly expressed in the hypertrophic cell zone and osteoblasts in condyle; 2) Dmp1 conventional KO display striking condyle phenotype, including malformed condyle without an apparent edge between condyle head and neck, and expanded hypertrophic chondrocytes, which was fully rescued by either a high Pi diet or injections of neutralized FGF23 antibodies, although alveolar bone phenotype remains; 3) Dmp1 cKO mice (by Col X-Cre) led to no grass changes in condyle.

Conclusion: DMP1 has no direct role in condyle cartilage, and Dmp1-null condyle phenotype is secondary to Pi changes.

This abstract is based on research that was funded entirely or partially by an outside source: NIH grant DE018486; China Scholarship Council to Qi Zhang

Keywords: Growth & development and Proteins
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