ArticleThe Journal of clinical investigation2019
Salt-inducible kinases dictate parathyroid hormone 1 receptor action in bone development and remodeling.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 49 citations in OpenAlex.
- Inhibition of salt-inducible kinases reprograms T cells and antitumor immunity in ovarian cancer.Nature immunology · 2026Article
- The orally available SIK2/SIK3 inhibitor SK-124 increases bone mass in hypogonadal male mice.JBMR plus · 2026Article
- The Role of the Salt-inducible Kinases in the Endocrine Glands.Endocrinology · 2025Review
- Control of alveolar bone development, homeostasis, and socket healing by salt-inducible kinases.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025Article
- Salt-inducible Kinase Regulation of Adipose Tissue Metabolism.Endocrinology · 2025Review
- Biomimetic Microstructured Scaffold with Release of Re-Modified Teriparatide for Osteoporotic Tendon-to-Bone Regeneration via Balancing Bone Homeostasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Characterization and preparation of food-derived peptides on improving osteoporosis: A review.Food chemistry: X · 2024Article
- SIK2 and SIK3 Differentially Regulate Mouse Granulosa Cell Response to Exogenous Gonadotropins In Vivo.Endocrinology · 2024Article
- Stimulation of fracture mineralization by salt-inducible kinase inhibitors.Frontiers in bioengineering and biotechnology · 2024Article
- Unveiling the Role of Sik1 in Osteoblast Differentiation: Implications for Osteoarthritis.Molecular and cellular biology · 2024Article
- Effects of antiresorptive medications on tooth root formation and tooth eruption in paediatric patients.Orthodontics & craniofacial research · 2023Review
- Effects of PTH on osteoblast bioenergetics in response to glucose.Bone reports · 2023Article
- Article
- The multiple roles of salt-inducible kinases in regulating physiology.Physiological reviews · 2023Review
- A parathyroid hormone/salt-inducible kinase signaling axis controls renal vitamin D activation and organismal calcium homeostasis.The Journal of clinical investigation · 2023Article
- Article
- Structure-based design of selective, orally available salt-inducible kinase inhibitors that stimulate bone formation in mice.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- PTHrP promotes subchondral bone formation in TMJ-OA.International journal of oral science · 2022Article
- NACA and LRP6 Are Part of a Common Genetic Pathway Necessary for Full Anabolic Response to Intermittent PTH.International journal of molecular sciences · 2022Article
- The osteocyte as a signaling cell.Physiological reviews · 2022Review
Corrections and comments
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Authors and funding
20 authors at 7 institutions in 3 countries.
Funding
Abstract
The parathyroid hormone 1 receptor (PTH1R) mediates the biologic actions of parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP). Here, we showed that salt-inducible kinases (SIKs) are key kinases that control the skeletal actions downstream of PTH1R and that this GPCR, when activated, inhibited cellular SIK activity. Sik gene deletion led to phenotypic changes that were remarkably similar to models of increased PTH1R signaling. In growth plate chondrocytes, PTHrP inhibited SIK3, and ablation of this kinase in proliferating chondrocytes rescued perinatal lethality of PTHrP-null mice. Combined deletion of Sik2 and Sik3 in osteoblasts and osteocytes led to a dramatic increase in bone mass that closely resembled the skeletal and molecular phenotypes observed when these bone cells express a constitutively active PTH1R that causes Jansen's metaphyseal chondrodysplasia. Finally, genetic evidence demonstrated that class IIa histone deacetylases were key PTH1R-regulated SIK substrates in both chondrocytes and osteocytes. Taken together, our findings establish that SIK inhibition is central to PTH1R action in bone development and remodeling. Furthermore, this work highlights the key role of cAMP-regulated SIKs downstream of GPCR action.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.