ArticleThe Journal of clinical investigation2019
Subchondral bone osteoclasts induce sensory innervation and osteoarthritis pain.
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 302 papers, 1 of them a synthesis that pooled it.
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Who cites it
302 citing papers in PubMed, 1 synthesis or guideline pooled it, 440 citations in OpenAlex.
- The causal effect of cytokine cycling levels on osteoarthritis: a bidirectional Mendelian randomized study.Frontiers in immunology · 2023Pooled it
- Effectiveness of extracorporeal shock wave therapy on functional ability in grade IV knee osteoarthritis - a randomized controlled trial.Scientific reports · 2024Trial
- A clinical model to predict the progression of knee osteoarthritis: data from Dryad.Journal of orthopaedic surgery and research · 2023Trial
- An osteogenesis mimicking biomineralized bone adhesive for rapid skeletal regeneration.Bioengineering & translational medicine · 2026Article
- Sensing the skeleton: sensorineural regulation in bone.Nature reviews. Neuroscience · 2026Review
- Multi-Omics Integration Identifies PTGS2 as a Candidate Diagnostic Biomarker and Precise Therapeutic Target Related to Schisandra chinensis for Osteoarthritis.Chemical biology & drug design · 2026Article
- Metabolic disorders and osteoarthritis: novel insights into pathological mechanisms and therapeutic strategies.Life medicine · 2026Review
- Lactate regulates osteoclastogenesis via H3k18la in osteoarthritis.International journal of molecular medicine · 2026Article
- Controlled release of CD200 inhibits inflammatory macrophages and chondrocyte catabolism.npj biomedical innovations · 2026Article
- Mechanistic Links Underlying the Comorbidity of Osteoporosis and Osteoarthritis: Cell Fate Plasticity Driven by the Subchondral Bone Microenvironment.International journal of molecular sciences · 2026Review
- KPT-330 alleviates osteoarthritis by inhibiting subchondral bone osteoclastogenesis via the NF-κB and MAPK signaling pathways.iScience · 2026Article
- Synovial macrophage-targeted hierarchical microspheres achieve cartilage preservation and pain relief in osteoarthritis.Materials today. Bio · 2026Article
- Osteoclast Heterogeneity in Osteoarthritis: From Single-Cell Microenvironments to Program-Specific Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Three-dimensional visualization of nerves in bones of the human hand in osteoarthritis.JBMR plus · 2026Article
- Neural regulation of bone: from central neural circuits to peripheral innervation of the skeletal stem cell niche.Bone research · 2026Review
- Review
- Review
- Mechanistic insights into cartilage-sensory nerve crosstalk in osteoarthritis progression.Journal of orthopaedic translation · 2026Review
- Disruption of the microenvironmental ecosystem in subchondral bone marrow lesions: Roles in osteoarthritis pathophysiology, pain and progression.Osteoarthritis imaging · 2026Article
- Systemic cachexia and muscle-bone crosstalk drive depression-related joint remodeling and pain.International journal of surgery (London, England) · 2026Article
242 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
28 authors at 6 institutions in 3 countries.
Funding
Abstract
Joint pain is the defining symptom of osteoarthritis (OA) but its origin and mechanisms remain unclear. Here, we investigated an unprecedented role of osteoclast-initiated subchondral bone remodeling in sensory innervation for OA pain. We show that osteoclasts secrete netrin-1 to induce sensory nerve axonal growth in subchondral bone. Reduction of osteoclast formation by knockout of receptor activator of nuclear factor kappa-B ligand (Rankl) in osteocytes inhibited the growth of sensory nerves into subchondral bone, dorsal root ganglion neuron hyperexcitability, and behavioral measures of pain hypersensitivity in OA mice. Moreover, we demonstrated a possible role for netrin-1 secreted by osteoclasts during aberrant subchondral bone remodeling in inducing sensory innervation and OA pain through its receptor DCC (deleted in colorectal cancer). Importantly, knockout of Netrin1 in tartrate-resistant acid phosphatase-positive (TRAP-positive) osteoclasts or knockdown of Dcc reduces OA pain behavior. In particular, inhibition of osteoclast activity by alendronate modifies aberrant subchondral bone remodeling and reduces innervation and pain behavior at the early stage of OA. These results suggest that intervention of the axonal guidance molecules (e.g., netrin-1) derived from aberrant subchondral bone remodeling may have therapeutic potential for OA pain.
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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.