ArticleCell death & disease2019
Salt-inducible kinase 1 regulates bone anabolism via the CRTC1-CREB-Id1 axis.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Integrating intrinsic musculoskeletal pathology and genetics: Recent advances in unravelling the causative factors of adolescent idiopathic scoliosis.Bone reports · 2025Review
- Increased TMEM106B levels lead to lysosomal dysfunction which affects synaptic signaling and neuronal health.Molecular neurodegeneration · 2025Article
- Integrated Bioinformatics and Experimental Validation Reveal Macrophage Polarization-Related Biomarkers for Osteoarthritis Diagnosis.Journal of multidisciplinary healthcare · 2025Article
- SIK1 inhibits IL-1β-stimulated cartilage apoptosis and inflammationOpen life sciences · 2025Article
- 'QuickDASH' to find unique genes and biological processes associated with shoulder osteoarthritis: a prospective case-control study.BMC research notes · 2024Article
- Unique expression and critical role of metallothionein 3 in the control of osteoclastogenesis and osteoporosis.Experimental & molecular medicine · 2024Article
- Cell signaling and transcriptional regulation of osteoblast lineage commitment, differentiation, bone formation, and homeostasis.Cell discovery · 2024Review
- Unveiling the Role of Sik1 in Osteoblast Differentiation: Implications for Osteoarthritis.Molecular and cellular biology · 2024Article
- Identification of Diagnostic Markers in Synovial Tissue of Osteoarthritis by Weighted Gene Coexpression Network.Biochemical genetics · 2023Article
- Deficiency of salt-inducible kinase 2 (SIK2) promotes immune injury by inhibiting the maturation of lymphocytes.MedComm · 2023Article
- The multiple roles of salt-inducible kinases in regulating physiology.Physiological reviews · 2023Review
- Study on the Mechanism of miR-146a in Gingival Mesenchymal Stem Cells.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Transcriptomic Analysis Provides Insights to Reveal theFrontiers in cell and developmental biology · 2022Article
- Effects of the Lysine Methyltransferase Inhibitor AZ505 on Bone Metabolism.Journal of bone metabolism · 2021Article
- Kinase drug discovery 20 years after imatinib: progress and future directions.Nature reviews. Drug discovery · 2021Review
- Article
- Excessive salt consumption causes systemic calcium mishandling and worsens microarchitecture and strength of long bones in rats.Scientific reports · 2021Article
- The potent roles of salt-inducible kinases (SIKs) in metabolic homeostasis and tumorigenesis.Signal transduction and targeted therapy · 2020Review
- CircAMOTL1 Promotes Tumorigenesis Through miR-526b/SIK2 Axis in Cervical Cancer.Frontiers in cell and developmental biology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
New bone anabolic agents for the effective treatment of bone metabolic diseases like osteoporosis are of high clinical demand. In the present study, we reveal the function of salt-inducible kinase 1 (SIK1) in regulating osteoblast differentiation. Gene knockdown of SIK1 but not of SIK2 or SIK3 expression in primary preosteoblasts increased osteoblast differentiation and bone matrix mineralization. SIK1 also regulated the proliferation of osteoblastic precursor cells in osteogenesis. This negative control of osteoblasts required the catalytic activity of SIK1. SIK1 phosphorylated CREB regulated transcription coactivator 1 (CRTC1), preventing CRTC1 from enhancing CREB transcriptional activity for the expression of osteogenic genes like Id1. Furthermore, SIK1 knockout (KO) mice had higher bone mass, osteoblast number, and bone formation rate versus littermate wild-type (WT) mice. Preosteoblasts from SIK1 KO mice showed more osteoblastogenic potential than did WT cells, whereas osteoclast generation among KO and WT precursors was indifferent. In addition, bone morphogenic protein 2 (BMP2) suppressed both SIK1 expression as well as SIK1 activity by protein kinase A (PKA)-dependent mechanisms to stimulate osteogenesis. Taken together, our results indicate that SIK1 is a key negative regulator of preosteoblast proliferation and osteoblast differentiation and that the repression of SIK1 is crucial for BMP2 signaling for osteogenesis. Therefore, we propose SIK1 to be a useful therapeutic target for the development of bone anabolic strategies.
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