ArticleCellular and molecular life sciences : CMLS2017
Mechanosensor polycystin-1 potentiates differentiation of human osteoblastic cells by upregulating Runx2 expression via induction of JAK2/STAT3 signaling axis.
Article in Cellular and molecular life sciences : CMLS, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 61 citations in OpenAlex.
- The Important Role of Polycystin in the Skeletal System.Calcified tissue international · 2026Review
- The Mechanism of Action of Stigmasterol in Bone Formation in Osteoporosis.Current issues in molecular biology · 2026Article
- Polycystin-1 Orchestrates Tumor Context-Dependent Mechanotransduction Programs Driving Epithelial-to-Mesenchymal Transition and Invasion in Solid Cancers.International journal of biological sciences · 2026Article
- Identification and validation of ferroptosis-related key hub genes linking hypoxia and osteoporosis.BMC musculoskeletal disorders · 2025Article
- Leptin receptor signaling mediates the distinct tendon-bone interface reconstruction in rotator cuff tears and osteoporosis-comorbid rotator cuff tears.Stem cell research & therapy · 2025Article
- Network Pharmacology and Experimental Validation of the Therapeutic Effect of Baji Capsule on LPS-Induced Osteoporosis.Orthopedic research and reviews · 2025Article
- Progress on the mechanism of Polycystin-1 in bone remodeling.Frontiers in cell and developmental biology · 2025Review
- Mechanical protein polycystin-1 directly regulates osteoclastogenesis and bone resorption.Science bulletin · 2024Article
- Runx2 and Polycystins in Bone Mechanotransduction: Challenges for Therapeutic Opportunities.International journal of molecular sciences · 2024Review
- Titanium Surfaces with a Laser-Produced Microchannel Structure Enhance Pre-Osteoblast Proliferation, Maturation, and Extracellular Mineralization In Vitro.International journal of molecular sciences · 2024Article
- The Role of Mechanotransduction in Contact Inhibition of Locomotion and Proliferation.International journal of molecular sciences · 2024Review
- Contribution of Signal Transducer and Activator of Transcription 3 (STAT3) to Bone Development and Repair.International journal of molecular sciences · 2023Article
- JAK/STAT pathway: Extracellular signals, diseases, immunity, and therapeutic regimens.Frontiers in bioengineering and biotechnology · 2023Review
- STAT3-mediated osteogenesis and osteoclastogenesis in osteoporosis.Cell communication and signaling : CCS · 2022Review
- Polycystin-1 regulates cell proliferation and migration through AKT/mTORC2 pathway in a human craniosynostosis cell model.Journal of cellular and molecular medicine · 2022Article
- Kindlin-2 preserves integrity of the articular cartilage to protect against osteoarthritis.Nature aging · 2022Article
- FRET Visualization of Cyclic Stretch-Activated ERKFrontiers in cell and developmental biology · 2022Article
- Peripheral Blood Mononuclear Cells (PBMCs) to Dissect the Underlying Mechanisms of Bone Disease in Chronic Kidney Disease and Rare Renal Diseases.Current osteoporosis reports · 2021Review
- PKD1 alleviates oxidative stress-inhibited osteogenesis of rat bone marrow-derived mesenchymal stem cells through TAZ activation.Journal of cellular biochemistry · 2021Article
- Role of KInternational journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Polycystin-1 (PC1) has been proposed as a chief mechanosensing molecule implicated in skeletogenesis and bone remodeling. Mechanotransduction via PC1 involves proteolytic cleavage of its cytoplasmic tail (CT) and interaction with intracellular pathways and transcription factors to regulate cell function. Here we demonstrate the interaction of PC1-CT with JAK2/STAT3 signaling axis in mechanically stimulated human osteoblastic cells, leading to transcriptional induction of Runx2 gene, a master regulator of osteoblastic differentiation. Primary osteoblast-like PC1-expressing cells subjected to mechanical-stretching exhibited a PC1-dependent increase of the phosphorylated(p)/active form of JAK2. Specific interaction of PC1-CT with pJAK2 was observed after stretching while pre-treatment of cells with PC1 (anti-IgPKD1) and JAK2 inhibitors abolished JAK2 activation. Consistently, mechanostimulation triggered PC1-mediated phosphorylation and nuclear translocation of STAT3. The nuclear phosphorylated(p)/DNA-binding competent pSTAT3 levels were augmented after stretching followed by elevated DNA-binding activity. Pre-treatment with a STAT3 inhibitor either alone or in combination with anti-IgPKD1 abrogated this effect. Moreover, PC1-mediated mechanostimulation induced elevation of Runx2 mRNA levels. ChIP assays revealed direct regulation of Runx2 promoter activity by STAT3/Runx2 after mechanical-stretching that was PC1-dependent. Our findings show that mechanical load upregulates expression of Runx2 gene via potentiation of PC1-JAK2/STAT3 signaling axis, culminating to possibly control osteoblastic differentiation and ultimately bone formation.
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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.