| Title: |
Control of alveolar bone development, homeostasis, and socket healing by salt inducible kinases |
| Authors: |
Tokavanich, Nicha; Chan, Byron; Strauss, Katelyn; Castro Andrade, Christian; Arai, Yuki; Nagata, Mizuki; Foretz, Marc; Brooks, Daniel; Ono, Noriaki; Ono, Wanida; Wein, Marc |
| Contributors: |
Université Paris Cité (UPCité); THALES France |
| Source: |
ISSN: 2692-8205 ; BioRxiv ; https://hal.science/hal-04791787 ; BioRxiv, 2024, ⟨10.1101/2024.09.04.611228⟩. |
| Publisher Information: |
CCSD; BioRxiv |
| Publication Year: |
2024 |
| Subject Terms: |
[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry; Molecular Biology/Biochemistry [q-bio.BM]; [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry; Molecular Biology/Molecular biology; [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism |
| Description: |
International audience ; 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 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. Summary statement 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/39282451; BIORXIV: 2024.09.04.611228; PUBMED: 39282451; PUBMEDCENTRAL: PMC11398370 |
| DOI: |
10.1101/2024.09.04.611228 |
| Availability: |
https://hal.science/hal-04791787; https://hal.science/hal-04791787v1/document; https://hal.science/hal-04791787v1/file/2024.09.04.611228v1.full.pdf; https://doi.org/10.1101/2024.09.04.611228 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.8768888A |
| Database: |
BASE |