ArticleArthritis and rheumatism2010
Chondrocyte innate immune myeloid differentiation factor 88-dependent signaling drives procatabolic effects of the endogenous Toll-like receptor 2/Toll-like receptor 4 ligands low molecular weight hyaluronan and high mobility group box chromosomal protein 1 in mice.
Article in Arthritis and rheumatism, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled it.
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Who cites it
92 citing papers in PubMed, 1 synthesis or guideline pooled it, 132 citations in OpenAlex.
- Tetracycline use in treating osteoarthritis: a systematic review.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2021Pooled it
- Bovine lactoferricin-induced anti-inflammation is, in part, via up-regulation of interleukin-11 by secondary activation of STAT3 in human articular cartilage.The Journal of biological chemistry · 2013Trial
- Bridging Scales: Integrating Hyaluronan-Based Nanoencapsulation into 3D Hydrogel Constructs for Advanced Therapeutics-A Comprehensive Review.Gels (Basel, Switzerland) · 2026Review
- Cellular Products with Anti-Inflammatory Properties for the Treatment of Cartilage Lesions.International journal of molecular sciences · 2026Review
- Contribution of insulin‑like growth factor‑1 to tendon repair (Review).International journal of molecular medicine · 2025Review
- Early diagnosis and targeted intervention based on the pathogenesis of rapidly progressive osteoarthritis of the hip.World journal of orthopedics · 2025Review
- Clinical and molecular landscape of post-traumatic osteoarthritis.Connective tissue research · 2025Review
- Follow the Molecule from Crystal Arthropathy to Comorbidities: The 2024 G-CAN Gold Medal Award Awardee Lecture.Gout, urate, and crystal deposition disease · 2025Article
- HMGB1 as an emerging key modulator of bone remodeling: a narrative review.Stem cell research & therapy · 2025Review
- Osteoimmunology in Osteoarthritis: Unraveling the Interplay of Immunity, Inflammation, and Joint Degeneration.Journal of inflammation research · 2025Review
- Catabolic mediators from TLR2-mediated proteoglycan aggrecan peptide-stimulated chondrocytes are reduced by Lactobacillus-conditioned media.Scientific reports · 2024Article
- Therapeutic Implication of miRNAs as an Active Regulatory Player in the Management of Pain: A Review.Genes · 2024Review
- The experimental study of mir-99a-5p negative regulation of TLR8 receptor mediated-mediated innate immune response in rabbit knee cartilage injury.Immunity, inflammation and disease · 2024Article
- Inhibition of TLR4 signalling to dampen joint inflammation in osteoarthritis.Rheumatology (Oxford, England) · 2024Review
- Efficient Generation of Chondrocytes From Bone Marrow-Derived Mesenchymal Stem Cells in a 3D Culture System: Protocol for a Practical Model for Assessing Anti-Inflammatory Therapies.JMIR research protocols · 2023Article
- Engineering Inflammation-Resistant Cartilage: Bridging Gene Therapy and Tissue Engineering.Advanced healthcare materials · 2023Article
- Tendon-regulating and bone-setting manipulation promotes the recovery of synovial inflammation in rabbits with knee osteoarthritis via the TLR4-MyD88-NF-κB signaling pathway.Annals of translational medicine · 2023Article
- Low molecular weight hyaluronan inhibits lung epithelial ion channels by activating the calcium-sensing receptor.Matrix biology : journal of the International Society for Matrix Biology · 2023Article
- Organellar homeostasis and innate immune sensing.Nature reviews. Immunology · 2022Review
- Remodeling Osteoarthritic Articular Cartilage under Hypoxic Conditions.International journal of molecular sciences · 2022Review
32 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
objectiveToll-like receptor 2 (TLR-2)/TLR-4-mediated innate immunity serves as a frontline antimicrobial host defense, but also modulates tissue remodeling and repair responses to endogenous ligands released during low-grade inflammation. We undertook the present study to assess whether the endogenous TLR-2/TLR-4 ligands low molecular weight hyaluronan (LMW-HA) and high mobility group box chromosomal protein 1 (HMGB-1), which are increased in osteoarthritic (OA) joints, drive procatabolic chondrocyte responses dependent on TLR-2 and TLR-4 signaling through the cytosolic adaptor myeloid differentiation factor 88 (MyD88).
methodsWe studied mature femoral head cap cartilage explants and immature primary knee articular chondrocytes from TLR-2/TLR-4-double-knockout, MyD88-knockout, and congenic wild-type mice. Generation of nitric oxide (NO), degradation of hyaluronan, release of HMGB-1, matrix metalloproteinase 3 (MMP-3), and MMP-13, and protein expression of type X collagen were assessed by Griess reaction and Western blotting analyses. Expression of messenger RNA for type II and type X collagen, MMP-13, and RUNX-2 was examined by real-time quantitative reverse transcription-polymerase chain reaction.
resultsInterleukin-1beta and TLR-2 and TLR-4 ligands induced both HMGB-1 release from chondrocytes and extracellular LMW-HA generation in normal chondrocytes. TLR-2/TLR-4(-/-) and MyD88(-/-) mouse cartilage explants and chondrocytes lost the capacity to mount procatabolic responses to both LMW-HA and HMGB-1, demonstrated by >95% suppression of NO production (P < 0.01), and attenuated induction of MMP-3 and MMP-13. Combined deficiency of TLR-2/TLR-4, or of MyD88 alone, also attenuated release of NO and blunted induction of MMP-3 and MMP-13 release. MyD88 was necessary for HMGB-1 and hyaluronidase 2 (which generates LMW-HA) to induce chondrocyte hypertrophy, which is implicated in OA progression.
conclusionMyD88-dependent TLR-2/TLR-4 signaling is essential for procatabolic responses to LMW-HA and HMGB-1, and MyD88 drives chondrocyte hypertrophy. Therefore, LMW-HA and HMGB-1 act as innate immune cytokine-like signals with the potential to modulate chondrocyte differentiation and function in OA progression.
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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.