Control of alveolar bone development, homeostasis, and socket healing by salt inducible kinases

• Published in: bioRxiv
• Main Authors: Tokavanich, Nicha, Chan, Byron, Strauss, Katelyn, Castro Andrade, Christian D, Arai, Yuki, Nagata, Mizuki, Foretz, Marc, Brooks, Daniel J, Ono, Noriaki, Ono, Wanida, Wein, Marc N
• Format: Journal Article
• Language: English
• Published: United States 06.09.2024
• ISSN: 2692-8205; 2692-8205
• DOI: 10.1101/2024.09.04.611228

Alveolar bone supports and anchors teeth. The parathyroid hormone-related protein (PTHrP) pathway plays a key role in alveolar bone biology. Salt inducible kinases (SIKs) are important downstream regulators of PTH/PTHrP signaling in the appendicular skeleton where SIK inhibition increases bone formation and trabecular bone mass. However, the function of these kinases in alveolar bone remains unknown. Here, we report a critical role for SIK2/SIK3 in alveolar bone development, homeostasis, and socket healing after tooth extraction. Inducible SIK2/SIK3 deletion led to dramatic alveolar bone defects without changes in tooth eruption. Ablating these kinases impairs alveolar bone formation due to disrupted osteoblast maturation, a finding associated with ectopic periostin expression by fibrous cells in regions of absent alveolar bone at steady state and following molar extraction. Distinct phenotypic consequences of SIK2/SIK3 deletion in appendicular versus craniofacial bones prompted us to identify a specific transcriptomic signature in alveolar versus long bone osteoblasts. Thus, SIK2/SIK3 deletion illuminates a key role for these kinases in alveolar bone biology and highlights the emerging concept that different osteoblast subsets utilize unique genetic programs. SIK2/SIK3 deletion in alveolar bone reduces bone formation and mass by impairing osteoblast maturation, unlike in long bones, where it increases bone formation and mass.