Sclerostin deficiency effectively promotes bone morphogenetic protein‐2‐induced ectopic bone formation

• Published in: Journal of periodontal research Vol. 58; no. 4; pp. 769 - 779
• Main Authors: Nakamura, Keigo, Koide, Masanori, Kobayashi, Yasuhiro, Yamashita, Teruhito, Matsushita, Mai, Yasuda, Hisataka, Ishihara, Yuichi, Yoshinari, Nobuo, Udagawa, Nobuyuki
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.08.2023
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Alveolar bone; Animals; BMP‐2; Bone density; Bone growth; Bone loss; Bone mass; Bone mineral density; Bone Morphogenetic Protein 2 - metabolism; Bone morphogenetic proteins; Bone resorption; Bones; Computed tomography; ectopic bone; Fractures; Glycoproteins - metabolism; Intercellular Signaling Peptides and Proteins - metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Ossification (ectopic); osteocyte; Osteocytes; Osteogenesis; osterix; Periodontal diseases; Periodontitis; Regeneration; sclerostin; SOST protein; Wnt protein; X-Ray Microtomography; osteocyte; BMP-2; ectopic bone; osterix; sclerostin
• ISSN: 0022-3484; 1600-0765
• DOI: 10.1111/jre.13134

Background and Objective Severe periodontitis causes alveolar bone resorption, resulting in tooth loss. Developments of tissue regeneration therapy that can restore alveolar bone mass are desired for periodontal disease. The application of bone morphogenetic protein‐2 (BMP‐2) has been attempted for bone fractures and severe alveolar bone loss. BMP‐2 reportedly induces sclerostin expression, an inhibitor of Wnt signals, that attenuates bone acquisition. However, the effect of sclerostin‐deficiency on BMP‐2‐induced bone regeneration has not been fully elucidated. We investigated BMP‐2‐induced ectopic bones in Sost‐knockout (KO) mice. Methods rhBMP‐2 were implanted into the thighs of C57BL/6 (WT) and Sost‐KO male mice at 8 weeks of age. The BMP‐2‐induced ectopic bones in these mice were examined on days 14 and 28 after implantation. Results Immunohistochemical and quantitative RT‐PCR analyses showed that BMP‐2‐induced ectopic bones expressed sclerostin in osteocytes on days 14 and 28 after implantation in Sost‐Green reporter mice. Micro‐computed tomography analysis revealed that BMP‐2‐induced ectopic bones in Sost‐KO mice showed a significant increased relative bone volume and bone mineral density (WT = 468 mg/cm3, Sost‐KO = 602 mg/cm3) compared with those in WT mice on day 14 after implantation. BMP‐2‐induced ectopic bones in Sost‐KO mice showed an increased horizontal cross‐sectional bone area on day 28 after implantation. Immunohistochemical staining showed that BMP‐2‐induced ectopic bones in Sost‐KO mice had an increased number of osteoblasts with osterix‐positive nuclei compared with those in WT mice on days 14 and 28 after implantation. Conclusion Sclerostin deficiency increased bone mineral density in BMP‐2‐induced ectopic bones.