ArticleThe Journal of biological chemistry2008
Polycystin-1 regulates skeletogenesis through stimulation of the osteoblast-specific transcription factor RUNX2-II.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
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- Progress on the mechanism of Polycystin-1 in bone remodeling.Frontiers in cell and developmental biology · 2025Review
- Advanced Piezoelectric Materials, Devices, and Systems for Orthopedic Medicine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Mechanical protein polycystin-1 directly regulates osteoclastogenesis and bone resorption.Science bulletin · 2024Article
- Autosomal Dominant Polycystic Kidney Disease: Extrarenal Involvement.International journal of molecular sciences · 2024Review
- Mechanosensitive protein polycystin-1 promotes periosteal stem/progenitor cells osteochondral differentiation in fracture healing.Theranostics · 2024Article
- Genetic interactions between polycystin-1 and Wwtr1 in osteoblasts define a novel mechanosensing mechanism regulating bone formation in mice.Bone research · 2023Article
- Convergence of Calcium Channel Regulation and Mechanotransduction in Skeletal Regenerative Biomaterial Design.Advanced healthcare materials · 2023Review
- Bone health in autosomal dominant polycystic kidney disease (ADPKD) patients after kidney transplantation.Bone reports · 2023Article
- Recent advances in primary cilia in bone metabolism.Frontiers in endocrinology · 2023Review
- [Low-frequency pulsed electromagnetic fields promote osteoblast mineralization and maturation of rats through the PC2/sAC/PKA/CREB signaling pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
- PKD1 alleviates oxidative stress-inhibited osteogenesis of rat bone marrow-derived mesenchymal stem cells through TAZ activation.Journal of cellular biochemistry · 2021Article
- Review
- Novel Small Molecule Fibroblast Growth Factor 23 Inhibitors Increase Serum Phosphate and Improve Skeletal Abnormalities inMolecular pharmacology · 2021Article
- Genetic variant of TTLL11 gene and subsequent ciliary defects are associated with idiopathic scoliosis in a 5-generation UK family.Scientific reports · 2021Article
- A cut above (and below): Protein cleavage in the regulation of polycystin trafficking and signaling.Cellular signalling · 2020Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Polycystin-1 (PC1) may play an important role in skeletogenesis through regulation of the bone-specific transcription factor Runx2-II. In the current study we found that PC1 co-localizes with the calcium channel polycystin-2 (PC2) in primary cilia of MC3T3-E1 osteoblasts. To establish the role of Runx2-II in mediating PC1 effects on bone, we crossed heterozygous Pkd1(m1Bei) and Runx2-II mice to create double heterozygous mice (Pkd1(+/m1Bei)/Runx2-II(+/-)) deficient in both PC1 and Runx2-II. Pkd1(+/m1Bei)/Runx2-II(+/-) mice exhibited additive reductions in Runx2-II expression that was associated with impaired endochondral bone development, defective osteoblast-mediated bone formation, and osteopenia. In addition, we found that basal intracellular calcium levels were reduced in homozygous Pkd1(m1Bei) osteoblasts. In contrast, overexpression of a PC1 C-tail construct increased intracellular calcium and selectively stimulated Runx2-II P1 promoter activity in osteoblasts through a calcium-dependent mechanism. Site-directed mutagenesis of critical amino acids in the coiled-coil domain of PC1 required for coupling to PC2 abolished PC1-mediated Runx2-II P1 promoter activity. Additional promoter analysis mapped the PC1-responsive region to the "osteoblast-specific" enhancer element between -420 and -350 bp that contains NFI and AP-1 binding sites. Chromatin immunoprecipitation assays confirmed the calcium-dependent binding of NFI to this region. These findings indicate that PC1 regulates osteoblast function through intracellular calcium-dependent control of Runx2-II expression. The overall function of the primary cilium-polycystin complex may be to sense and transduce environmental clues into signals regulating osteoblast differentiation and bone development.
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Registered trials
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