ArticleBone research2022
Kindlin-2 inhibits Nlrp3 inflammasome activation in nucleus pulposus to maintain homeostasis of the intervertebral disc.
Article in Bone research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 98 citations in OpenAlex.
- A nucleic acid regulation strategy under mechanical stress for intervertebral disc degeneration treatment.Bioactive materials · 2026Article
- A Decoy-Receptor-Armed Biomimetic Nanotherapeutic With Inherent Tropism for Conserved Pathogenic Macrophages for Treating Osteoarthritis and Intervertebral Disc Degeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Sustained Hypoxia-Inducible Factor 1-Alpha Accumulation Disrupts the Articular Niche to Promote Osteoarthritis Pathogenesis.Aging cell · 2026Article
- The vinculin-β-catenin axis promotes bone formation and repair: an essential prerequisite for the anti-osteoporotic efficacy of sclerostin-neutralizing antibody.Science China. Life sciences · 2026Article
- Pyroptosis: mechanism and therapeutic strategies with intervertebral disc degeneration.Experimental & molecular medicine · 2026Review
- Kindlins regulate integrin- and growth factor-dependent ureteric bud formation.Development (Cambridge, England) · 2026Article
- ROS-responsive biomaterial delivery of the TCM-derived small molecule coptisine protects stem cells and attenuates intervertebral disc degeneration.Frontiers in bioengineering and biotechnology · 2026Article
- IFT88/Kindlin-2 Signaling Prevents Mechanical Overloading-Induced PANoptosis of Nucleus Pulposus Cells by Activating FOXP1 SUMOylation.International journal of biological sciences · 2026Article
- Mechanotransduction in intervertebral disc degeneration: from compartment-specific sensors to translational frontiers.Frontiers in bioengineering and biotechnology · 2026Review
- Regulated cell death in musculoskeletal development, homeostasis, and diseases.Fundamental research · 2026Review
- Molecular mechanisms and therapeutic implications of the sympathetic nervous system in bone-related disorders: a brain-bone axis perspective.Bone research · 2025Review
- RIPK1-targeted therapy alleviates intervertebral disc degeneration via inhibiting nucleus pulposus PANoptosis.Apoptosis : an international journal on programmed cell death · 2025Article
- Targeting FABP4 to Inhibit AGEs-RAGE/NF-κB Signalling Effectively Ameliorates Nucleus Pulposus Dysfunction and Angiogenesis in Obesity-Related Intervertebral Disc Degeneration.Cell proliferation · 2025Article
- Osteocytic vinculin controls bone mass by modulating Mef2c-driven sclerostin expression in mice.Bone research · 2025Article
- TRIM29 alleviates intervertebral disc degeneration through the PI3K/AKT/mTOR pathway.Scientific reports · 2025Article
- Omeprazole exacerbates intervertebral disc degeneration through Caspase-3 mediated apoptosis of nucleus pulposus cells: a Mendelian randomization, network toxicology, and in vitro experimental study.Journal of orthopaedic surgery and research · 2025Article
- Upregulated CEMIP promotes intervertebral disc degeneration via AP-1-mediated change in chromatin accessibility.Clinical and translational medicine · 2025Article
- Microneedle delivery of CAR-M-like engineered macrophages alleviates intervertebral disc degeneration through enhanced efferocytosis capacity.Cell reports. Medicine · 2025Article
- Targeting Piezo1 channel to alleviate intervertebral disc degeneration.Journal of orthopaedic translation · 2025Article
- NLRP3 inflammasome in health and disease (Review).International journal of molecular medicine · 2025Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intervertebral disc (IVD) degeneration (IVDD) is the main cause of low back pain with major social and economic burdens; however, its underlying molecular mechanisms remain poorly defined. Here we show that the focal adhesion protein Kindlin-2 is highly expressed in the nucleus pulposus (NP), but not in the anulus fibrosus and the cartilaginous endplates, in the IVD tissues. Expression of Kindlin-2 is drastically decreased in NP cells in aged mice and severe IVDD patients. Inducible deletion of Kindlin-2 in NP cells in adult mice causes spontaneous and striking IVDD-like phenotypes in lumbar IVDs and largely accelerates progression of coccygeal IVDD in the presence of abnormal mechanical stress. Kindlin-2 loss activates Nlrp3 inflammasome and stimulates expression of IL-1β in NP cells, which in turn downregulates Kindlin-2. This vicious cycle promotes extracellular matrix (ECM) catabolism and NP cell apoptosis. Furthermore, abnormal mechanical stress reduces expression of Kindlin-2, which exacerbates Nlrp3 inflammasome activation, cell apoptosis, and ECM catabolism in NP cells caused by Kindlin-2 deficiency. In vivo blocking Nlrp3 inflammasome activation prevents IVDD progression induced by Kindlin-2 loss and abnormal mechanical stress. Of translational significance, adeno-associated virus-mediated overexpression of Kindlin-2 inhibits ECM catabolism and cell apoptosis in primary human NP cells in vitro and alleviates coccygeal IVDD progression caused by mechanical stress in rat. Collectively, we establish critical roles of Kindlin-2 in inhibiting Nlrp3 inflammasome activation and maintaining integrity of the IVD homeostasis and define a novel target for the prevention and treatment of IVDD.
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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.