Faculty, Staff and Student Publications

Language

English

Publication Date

5-24-2025

Journal

Journal of Bone and Mineral Research

DOI

10.1093/jbmr/zjaf038

PMID

40057979

PMCID

PMC12755032

PubMedCentral® Posted Date

1-1-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

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 (Ubq-creERt;Sik2f/f;Sik3f/f) 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. Notably, this phenotype is the opposite of the increased trabecular bone mass observed in long bones following SIK2/SIK3 deletion. 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.

Keywords

Animals, Homeostasis, Protein Serine-Threonine Kinases, Tooth Socket, Alveolar Process, Wound Healing, Mice, Osteoblasts, Tooth Extraction, Bone Development, Osteogenesis, Alveolar bone, salt-inducible kinases, osteoblast, tooth extraction, dental development

Published Open-Access

yes

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