Deficiency of the SMOC2 matricellular protein impairs bone healing and produces age-dependent bone loss - Archive ouverte HAL Access content directly
Journal Articles Scientific Reports Year : 2020

Deficiency of the SMOC2 matricellular protein impairs bone healing and produces age-dependent bone loss

Eric Mathieu
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Joseph Hemmerlé
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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.
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Dates and versions

hal-03663184 , version 1 (09-05-2022)

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Supawich Morkmued, François Clauss, Brigitte Schuhbaur, Valerie Fraulob, Eric Mathieu, et al.. Deficiency of the SMOC2 matricellular protein impairs bone healing and produces age-dependent bone loss. Scientific Reports, 2020, 10, pp.14817. ⟨10.1038/s41598-020-71749-6⟩. ⟨hal-03663184⟩
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