Abstract
Secreted extracellular matrix components which regulate craniofacial development could be reactivated and play roles in adult wound healing. We report a patient with a loss-of-function of the secreted matricellular protein SMOC2 (SPARC related modular calcium binding 2) presenting severe oligodontia, microdontia, tooth root deficiencies, alveolar bone hypoplasia, and a range of skeletal malformations. Turning to a mouse model, Smoc2-GFP reporter expression indicates SMOC2 dynamically marks a range of dental and bone progenitors. While germline Smoc2 homozygous mutants are viable, tooth number anomalies, reduced tooth size, altered enamel prism patterning, and spontaneous age-induced periodontal bone and root loss are observed in this mouse model. Whole-genome RNA-sequencing analysis of embryonic day (E) 14.5 cap stage molars revealed reductions in early expressed enamel matrix components (Odontogenic ameloblast-associated protein) and dentin dysplasia targets (Dentin matrix acidic phosphoprotein 1). We tested if like other matricellular proteins SMOC2 was required for regenerative repair. We found that the Smoc2-GFP reporter was reactivated in adjacent periodontal tissues 4 days after tooth avulsion injury. Following maxillary tooth injury, Smoc2−/− mutants had increased osteoclast activity and bone resorption surrounding the extracted molar. Interestingly, a 10-day treatment with the cyclooxygenase 2 (COX2) inhibitor ibuprofen (30 mg/kg body weight) blocked tooth injury-induced bone loss in Smoc2−/− mutants, reducing matrix metalloprotease (Mmp)9. Collectively, our results indicate that endogenous SMOC2 blocks injury-induced jaw bone osteonecrosis and offsets age-induced periodontal decay.
Highlights
Secreted extracellular matrix components which regulate craniofacial development could be reactivated and play roles in adult wound healing
We initially reported that SMOC2 deficiency severely disrupts tooth formation, as patients with a loss-of-function of this secreted matricellular protein display striking phenotypic defects in primary and permanent dentitions including microdontia, oligodontia, dysplastic root formation and alveolar bone hypoplasia[12]
While frontal and lateral radiographic views (Fig. 1A,B) of the skull showed no severe skull malformations, lumbar vertebrae were markedly flattened and the presence of a hyperlordotic curved spinal column suggested skeletal defects might worsen with age, just as wider iliac wings suggested a small degree of skeletal dysplasia (Supplementary Fig. S1D) not observed in other regions (Supplementary Fig. S1F)
Summary
Secreted extracellular matrix components which regulate craniofacial development could be reactivated and play roles in adult wound healing. We report a patient with a loss-of-function of the secreted matricellular protein SMOC2 (SPARC related modular calcium binding 2) presenting severe oligodontia, microdontia, tooth root deficiencies, alveolar bone hypoplasia, and a range of skeletal malformations. Patients with homozygous SMOC2 mutations have specific dental developmental defects These include oligodontia (reduced tooth number), microdontia (small teeth), short roots, dentin dysplasia, and reduced alveolar/jaw bone density[12,17]. Strategies modulating the SMOC2-induced secretome might improve alveolar bone repair following a number of dental treatments. This could be applied clinically to alleviate jaw osteonecrosis-like symptoms[18], a frequent decisive consequence of tooth extraction during bisphosphonate osteoporosis treatment
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
