ArticleBone research2019
Activation of mTORC1 in subchondral bone preosteoblasts promotes osteoarthritis by stimulating bone sclerosis and secretion of CXCL12.
Article in Bone research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 95 citations in OpenAlex.
- Spatial transcriptomics reveals microenvironmental heterogeneity in osteoarthritic subchondral bone.Nature communications · 2026Article
- Metabolic disorders and osteoarthritis: novel insights into pathological mechanisms and therapeutic strategies.Life medicine · 2026Review
- Cartilage targeted grape skin-derived extracellular vesicles ameliorate osteoarthritis by attenuating chondrocyte senescence.Journal of nanobiotechnology · 2026Article
- Injectable microgels carrying engineered biomimetic nanoparticles for osteoarthritis therapy via dual-targeted senescent chondrocyte clearance and endogenous repair promotion.Bioactive materials · 2026Article
- Local delivery of OSK factors enables partial cellular reprogramming to mitigate osteoarthritis and cartilage fibrosis.Experimental & molecular medicine · 2026Article
- Signaling pathways and ion channels in osteoarthritis: a review of recent advances.Frontiers in immunology · 2026Review
- Author Correction: Activation of mTORC1 in subchondral bone preosteoblasts promotes osteoarthritis by stimulating bone sclerosis and secretion of CXCL12.Bone research · 2025Article
- Fire needling acupuncture attenuates synovial inflammation and cartilage degeneration in knee osteoarthritis via SDF-1/CXCR4-mediated macrophage polarization.Clinical rheumatology · 2025Article
- RO5126766 attenuates osteoarthritis by inhibiting osteoclastogenesis and protecting chondrocytes through mediating the ERK pathway.Journal of orthopaedic translation · 2025Article
- Unravelling the ties that bind: The intersection of obesity, osteoarthritis, and inflammatory pathways with emphasis on glucagon-like peptide-1 agonists.Clinical obesity · 2025Review
- Therapeutic Effects of Fire Needling Acupuncture on Pain Relief and Cartilage Protection in MIA-Induced Knee Osteoarthritis Rats: The Role of Macrophage Polarization in Synovium and Angiogenesis in Subchondral Bone.Journal of inflammation research · 2025Article
- Tcirg1 deficiency delays osteoarthritis progression by impairing lysosome acidification and peripheral accumulation in osteoclasts.Frontiers in cell and developmental biology · 2025Article
- Identification of osteoblastic autophagy-related genes for predicting diagnostic markers in osteoarthritis.iScience · 2024Article
- Osteocytes/Osteoblasts Produce SAA3 to Regulate Hepatic Metabolism of Cholesterol.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Sipeimine ameliorates osteoarthritis progression by suppression of NLRP3 inflammasome-mediated pyroptosis through inhibition of PI3K/AKT/NF-κB pathway: An in vitro and in vivo study.Journal of orthopaedic translation · 2024Article
- Hydrophilic/Hydrophobic Janus Nanofibers Containing Compound K for Cartilage Regeneration.International journal of nanomedicine · 2024Article
- Deciphering the Role of LncRNAs in Osteoarthritis: Inflammatory Pathways Unveiled.Journal of inflammation research · 2024Review
- IgSF11 deficiency alleviates osteoarthritis in mice by suppressing early subchondral bone changes.Experimental & molecular medicine · 2023Article
- Exploring the translational potential of PLGA nanoparticles for intra-articular rapamycin delivery in osteoarthritis therapy.Journal of nanobiotechnology · 2023Article
- Comprehensive analysis on subchondral bone marrow lesions of human osteoarthritis by integrating bulk and single-cell transcriptomes.BMC musculoskeletal disorders · 2023Article
Corrections and comments
- Commented on by
- Erratum issued
- Erratum issued
Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increasing evidences show that aberrant subchondral bone remodeling plays an important role in the development of osteoarthritis (OA). However, how subchondral bone formation is activated and the mechanism by which increased subchondral bone turnover promotes cartilage degeneration during OA remains unclear. Here, we show that the mechanistic target of rapamycin complex 1 (mTORC1) pathway is activated in subchondral bone preosteoblasts (Osterix+) from OA patients and mice. Constitutive activation of mTORC1 in preosteoblasts by deletion of the mTORC1 upstream inhibitor, tuberous sclerosis 1, induced aberrant subchondral bone formation, and sclerosis with little-to-no effects on articular cartilage integrity, but accelerated post-traumatic OA development in mice. In contrast, inhibition of mTORC1 in preosteoblasts by disruption of Raptor (mTORC1-specific component) reduced subchondral bone formation and cartilage degeneration, and attenuated post-traumatic OA in mice. Mechanistically, mTORC1 activation promoted preosteoblast expansion and Cxcl12 secretion, which induced subchondral bone remodeling and cartilage degeneration during OA. A Cxcl12-neutralizing antibody reduced cartilage degeneration and alleviated OA in mice. Altogether, these findings demonstrate that mTORC1 activation in subchondral preosteoblasts is not sufficient to induce OA, but can induce aberrant subchondral bone formation and secrete of Cxcl12 to accelerate disease progression following surgical destabilization of the joint. Pharmaceutical inhibition of the pathway presents a promising therapeutic approach for OA treatment.
Identifiers
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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.