Differential effects of PTH, PTHrP and abaloparatide on collagen 1 expression by mouse cementoblasts and mouse tooth root density

• Published in: American journal of orthodontics and dentofacial orthopedics 2022-12, Vol.163 (3), p.378-388.e1
• Main Authors: Hsu, Chingyun, He, Zhiming, Le Henaff, Carole, Partridge, Nicola C.
• Format: Article
• Language: English
• ISSN: 0889-5406; 1097-6752
• DOI: 10.1016/j.ajodo.2021.12.023

Parathyroid hormone (PTH) plays an important role in maintaining mineral homeostasis, in part by regulating calcium and phosphate levels. Previously, clinical trials have shown that peptides of PTH (1–34), PTH related protein (PTHrP 1–36) and the new peptide modeled on PTHrP, abaloparatide, can have different anabolic effects on osteoporotic subjects, but the underlying mechanisms are still unclear. The prevalence of moderate and major gingival recession has been shown to be higher in postmenopausal women with osteoporosis. Also, there is a significant association between osteoporosis and tooth loss. Methods: We investigated the actions of these peptides on cementoblasts and teeth of mice. The murine cementoblast line, OCCM.30, known to express collagen I ( Col1a1 ), was treated with intermittent PTH (1–34), PTHrP (1–36) or abaloparatide for 6 hours every 24 hours for 3 days. MicroCT was done on the teeth of mice receiving daily injections of PBS, PTH (1–34) or abaloparatide. Statistical differences were analyzed by two-way or one-way ANOVA followed by Tukey’s post hoc test. Results are expressed as means ± S.D. and p < 0.05 was considered significant. Results: Gene expression showed regulation of Bsp , Col1a1 , Opg , Rankl and Mmp13 by the three peptides in these cells. Western blots revealed that after intermittent treatment for 3 days, PTH (1–34) caused an increase in COL1A1 protein immediately after treatment. In contrast, abaloparatide showed a latent effect in increasing COL1A1 protein 18 hours after treatment. PTHrP had no effect on COL1A1 protein. Immunofluorescence confirmed the same result as the Western blots. MicroCT of teeth showed PTH (1–34) injections increased molar root mineral density in mice while abaloparatide increased it in roots of both incisors and molars. Conclusion: This study reveals the differential anabolic effects of intermittent PTH (1–34), PTHrP (1–36) and abaloparatide on cementoblasts as revealed by collagen 1 protein expression and root mineral density. Abaloparatide may be a potential therapeutic approach for achieving improved cementogenesis.