Cilia-like Structures and Polycystin-1 in Osteoblasts/Osteocytes and Associated Abnormalities in Skeletogenesis and Runx2 Expression
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We examined the osteoblast/osteocyte expression and function of polycystin-1 (PC1), a transmembrane protein that is a component of the polycystin-2 (PC2)-ciliary mechano-sensor complex in renal epithelial cells. We found that MC3T3-E1 osteoblasts and MLO-Y4 osteocytes express transcripts for PC1, PC2, and the ciliary proteins Tg737 and Kif3a. Immunohistochemical analysis detected cilia-like structures in MC3T3-E1 osteoblastic and MLO-Y4 osteocyte-like cell lines as well as primary osteocytes and osteoblasts from calvaria. Pkd1m1Bei mice have inactivating missense mutations of Pkd1 gene that encode PC1. Pkd1m1Bei homozygous mutant mice demonstrated delayed endochondral and intramembranous bone formation, whereas heterozygous Pkd1m1Bei mutant mice had osteopenia caused by reduced osteoblastic function. Heterozygous and homozygous Pkd1m1Bei mutant mice displayed a gene dose-dependent decrease in the expression of Runx2 and osteoblast-related genes. In addition, overexpression of constitutively active PC1 C-terminal constructs in MC3T3-E1 osteoblasts resulted in an increase in Runx2 P1 promoter activity and endogenous Runx2 expression as well as an increase in osteoblast differentiation markers. Conversely, osteoblasts derived from Pkd1m1Bei homozygous mutant mice had significant reductions in endogenous Runx2 expression, osteoblastic markers, and differentiation capacity ex vivo. Co-expression of constitutively active PC1 C-terminal construct into Pkd1m1Bei homozygous osteoblasts was sufficient to normalize Runx2 P1 promoter activity. These findings are consistent with a possible functional role of cilia and PC1 in anabolic signaling in osteoblasts/osteocytes.
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A protein complex formed by a cilium and its associated proteins PolyCystins 1 and 2 has been suggested to be crucial for osteocyte mechanosensing and for osteoblast/osteocyte-mediated bone formation.
“One of them is that there is a protein complex formed by a cilium and its associated proteins PolyCystins 1 and 2, which has been suggested to be crucial for osteocyte mechanosensing and for osteoblast/osteocyte-mediated bone formation [78].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [78]
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- Authors
- Xiao, Z., Zhang, S., Mahlios, J., Zhou, G., Magenheimer, B. S., Guo, D., Dallas, S. L., Maser, R., Calvet, J. P., Bonewald, L., & Quarles, L. D.
- Affiliations
- University of Kansas Medical Center (US)
- Corresponding author
- Quarles, Leigh Darryl
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2006-10
- Volume
- 281
- Issue
- 41
- Pages
- 30884-30895
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC1797154
- OpenAlex
- W2082625064
- Cited by
- 254
- References
- 62
- Citations by year
- 2026: 8 · 2025: 4 · 2024: 7 · 2023: 9 · 2022: 10 · 2021: 13 · 2020: 17 · 2019: 14 · 2018: 6 · 2017: 12 · 2016: 9 · 2015: 9 · 2014: 11 · 2013: 18 · 2012: 16
- FWCI
- 10.06
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK083303, P50DK057301)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR049712, P01AR046798, P01AR46798)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
- Keywords
- polycystin-1, polycystin-2, primary cilia, osteoblasts, osteocytes, Runx2, PKD1, endochondral ossification, intramembranous ossification, osteogenic differentiation, osteopenia, KIF3A, calvaria
- MeSH terms
- Protein Kinase D2, Animals, Bone Development, Cells, Cultured, Cilia, Mice, Transgenic, Mutation, Osteoblasts, Osteocytes, Protein Kinases, Gene Expression Regulation, Developmental, TRPP Cation Channels, Core Binding Factor Alpha 1 Subunit, Mice
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