• Cartilage, Articular/growth & development
• Cartilage, Articular/physiology
• Humans
• Extracellular Matrix/physiology
• Extracellular Matrix/metabolism
• Tissue Engineering/methods
• Proteoglycans/metabolism
• Animals
• Collagen Type II/metabolism

• Humans
• Animals
• Bone and Bones/metabolism
• Bone and Bones/drug effects
• Indoles/pharmacology
• Indoles/metabolism
• Signal Transduction/drug effects
• Osteoblasts/drug effects
• Osteoblasts/metabolism

• macrophage polarization
• microneedle drug delivery
• osteoarthritis
• polydopamine‐exosome complex
• reactive oxygen species scavenging

• Osteoarthritis/drug therapy
• Osteoarthritis/metabolism
• Animals
• TOR Serine-Threonine Kinases/metabolism
• Proto-Oncogene Proteins c-akt/metabolism
• Polymers/chemistry
• Needles
• Disease Models, Animal
• Phosphatidylinositol 3-Kinases/metabolism
• Indoles
• Signal Transduction/drug effects
• Drug Delivery Systems/methods
• Mice
• Humans

• SHDSYY-2021-2297 Animal Health Care Ethics Committee of Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
• 2022YFC2009505 National Key R&D Program of China
• 22S31900300 Shanghai Committee of Science and Technology
• 21ZR1458500 Shanghai Committee of Science and Technology
• ITJ(ZD)2004 Shanghai Tongji Hospital
• RC20230035 Shanghai Jiaotong University Ruijin Hospital
• National Key R&D Program of China

• exosomes
• matrix-bound nanovesicles
• mesenchymal stromal cells
• monocyte-derived macrophages
• osteoarthritis

• Humans
• Mesenchymal Stem Cells/metabolism
• Exosomes/metabolism
• Umbilical Cord/cytology
• Animals
• Rats
• Osteoarthritis/therapy
• Osteoarthritis/metabolism
• Osteoarthritis/pathology
• Extracellular Vesicles/metabolism
• Extracellular Vesicles/transplantation
• Extracellular Matrix/metabolism
• Macrophages/metabolism
• Male
• Disease Models, Animal

• 075-15-2024-640 (Sechenov University) the Ministry of Science and Higher Education of the Russian Federation

• shoulder
• cartilage
• histology
• glenohumeral joints
• humeral heads
• collagen
• staining
• synovitis
• synovial tissues
• collagen type ii
• cuff tear arthropathy
• immunohistochemically

• Articular cartilage
• Disuse atrophy
• Mechanical loading
• Reversibility
• Subchondral bone

• Animals
• Cartilage, Articular/pathology
• Cartilage, Articular/metabolism
• Mice
• Chondrocytes/metabolism
• Chondrocytes/pathology
• ADAMTS5 Protein/metabolism
• ADAMTS5 Protein/genetics
• Hindlimb Suspension/adverse effects
• Stress, Mechanical
• Matrix Metalloproteinase 13/metabolism
• SOX9 Transcription Factor/metabolism
• SOX9 Transcription Factor/genetics
• Aggrecans/metabolism
• Collagen Type II/metabolism
• Male
• X-Ray Microtomography
• Weight-Bearing/physiology
• Atrophy
• Knee Joint/pathology
• Knee Joint/physiopathology
• Knee Joint/metabolism
• Mice, Inbred C57BL
• Disease Models, Animal
• Physical Conditioning, Animal

• Kobe University

• bioactive compounds
• cartilage
• chondrocyte
• epigenetics
• nutriepigenomics
• osteoarthritis

• PI19/01213 Instituto de Salud Carlos III

• CRISPR-Cas system
• Cartilage repair
• Cellular senescence
• Inflammation
• Osteoarthritis

• Humans
• Osteoarthritis/genetics
• Osteoarthritis/therapy
• CRISPR-Cas Systems/genetics
• Inflammation/genetics
• Gene Editing/methods
• Animals
• Genetic Therapy/methods
• Cartilage/metabolism
• Cartilage/pathology
• Cellular Senescence/genetics
• Cartilage, Articular/pathology
• Cartilage, Articular/metabolism

• SZSM202211019 Shenzhen"San-Ming" Project of Medicine
• 2023A1515220257 Basic and Applied Basic Research Foundation of Guangdong Province
• 2023A1515220019 Basic and Applied Basic Research Foundation of Guangdong Province
• 2022A1515220056 Basic and Applied Basic Research Foundation of Guangdong Province
• Shenzhen“San-Ming” Project of Medicine

• biological barriers
• drug delivery
• engineering
• extracellular vesicles
• therapy

• National Natural Science Foundation of China

• Chondrocyte
• Hedgehog pathway
• Osteoarthritis
• Ribosomal protein L35
• Senescence

• Atelocollagen scaffold
• BMAC
• Cartilage repair
• Microfracture
• Osteochondral defect

• Animals
• Male
• Rabbits
• Cartilage, Articular/pathology
• Collagen
• Tissue Scaffolds/chemistry
• Wound Healing

• Ferroptosis
• GPX4
• Nrf2
• Osteoarthritis
• Ruscogenin

• Animals
• Mice
• Cartilage/drug effects
• Cartilage/metabolism
• Cartilage/pathology
• Chondrocytes/drug effects
• Ferroptosis/drug effects
• Inflammation/metabolism
• Interleukin-1beta/metabolism
• Matrix Metalloproteinase 1/metabolism
• Matrix Metalloproteinase 3/genetics
• Matrix Metalloproteinase 3/metabolism
• NF-E2-Related Factor 2/metabolism
• Osteoarthritis/drug therapy
• Osteoarthritis/metabolism
• Signal Transduction
• Spirostans

• NF-κB
• apoptosis
• endoplasmic reticulum stress
• ganoderic acid A
• osteoarthritis

• Mice
• Animals
• NF-kappa B/metabolism
• Molecular Docking Simulation
• Osteoarthritis/drug therapy
• Osteoarthritis/metabolism
• Inflammation/drug therapy
• Inflammation/metabolism
• Chondrocytes/metabolism
• Endoplasmic Reticulum Stress
• Interleukin-1beta/metabolism
• Cells, Cultured
• Heptanoic Acids
• Lanosterol/analogs & derivatives

• 2022B996 Administration of Jiangxi Province Traditional Chinese Medicine
• G/Y2577 Double Thousand Plan Foundation of Jiangxi Province Human Resources and Social Security Department
• 2020ACBL206012 Key Intervertebral Disc Laboratory of Jiangxi Province
• 81860397 National Natural Science Foundation of China

• Chondrocytes
• GPR68
• Matrix degeneration
• Orphan receptor
• Osteoarthritis

• Humans
• Animals
• Mice
• Cartilage, Articular/metabolism
• Osteoarthritis/genetics
• Extracellular Matrix/genetics
• Receptors, G-Protein-Coupled/genetics
• GTP-Binding Proteins/metabolism
• Hydrogen-Ion Concentration

• R03 TR003669 NCATS NIH HHS

• Male
• Animals
• Mice
• Mice, Inbred C57BL
• Osteoarthritis, Knee/therapy
• Tumor Necrosis Factor-alpha
• Matrix Metalloproteinase 13/genetics
• Matrix Metalloproteinase 3
• Interleukin-6/genetics
• Vibration/therapeutic use
• Cartilage, Articular

• The National Natural Science Foundation of China
• the Project of the Science and Technology Department in Sichuan province
• Sichuan Provincial Department of Science and Technology Fund
• The Project of the Science and Technology Department in Henan Provincial Department
• The Joint project of Henan Provincial Health Commission
• The Natural Science Foundation of China-Henan Province
• Key Research Projects of Higher Education Institutions in Henan Province
• Henan Medical Education Research Project

• chondroitin sulfate
• chondroprotection
• joint health
• osteoarthritis
• supplementation

• Cartilage repair
• Meta-analysis
• Osteoarthritis
• Osteochondral lesion of talus
• Platelet-rich plasma
• Systematic review

• Gas6
• TAM receptors
• osteoarthritis
• synovitis

• 19-1-204 Reumafonds
• 001 Coordenação de Aperfeicoamento de Pessoal de Nível Superior

• chondrocyte
• mechanobiology
• mechanotransduction
• network-based model
• osteoarthritis
• systems biology

• Aromatic hydrocarbon receptor
• Chondrocytes
• Indole-3-propionic acid
• Inflammation
• Osteoarthritis

• Auranofin
• Extracellular matrix
• Nrf2 pathway
• Osteoarthritis
• TXNRD1

• Animals
• Mice
• Auranofin/pharmacology
• Cartilage, Articular/metabolism
• Chondrocytes/metabolism
• Extracellular Matrix/metabolism
• Interleukin-1beta/metabolism
• NF-E2-Related Factor 2/genetics
• NF-E2-Related Factor 2/metabolism
• Osteoarthritis/metabolism
• Thioredoxin Reductase 1/genetics

• Chondrogenesis
• DHA
• Inflammation
• Malat1
• NF-κB
• Osteoarthritis
• Wnt/β-catenin

Osteoarthritis (OA) alters chondrocyte metabolism and mitochondrial biology. We explored whether OA and non-OA chondrocytes show persistent differences in metabolism and mitochondrial function and different responsiveness to cytokines and cAMP modulators. Hip chondrocytes from patients with OA or femoral neck fracture (non-OA) were stimulated with IL-1β, TNF, forskolin and opioid peptides. Mediators released from chondrocytes were measured, and mitochondrial functions and glycolysis were determined (Seahorse Analyzer). Unstimulated OA chondrocytes exhibited significantly higher release of IL-6, PGE₂ and MMP1 and lower production of glycosaminoglycan than non-OA chondrocytes. Oxygen consumption rates (OCR) and mitochondrial ATP production were comparable in unstimulated non-OA and OA chondrocytes, although the non-mitochondrial OCR was higher in OA chondrocytes. Compared to OA chondrocytes, non-OA chondrocytes showed stronger responses to IL-1β/TNF stimulation, consisting of a larger decrease in mitochondrial ATP production and larger increases in non-mitochondrial OCR and NO production. Enhancement of cAMP by forskolin prevented IL-1β-induced mitochondrial dysfunction in OA chondrocytes but not in non-OA chondrocytes. Endogenous opioids, present in OA joints, influenced neither cytokine-induced mitochondrial dysfunction nor NO upregulation. Glycolysis was not different in non-OA and OA chondrocytes, independent of stimulation. OA induces persistent metabolic alterations, but the results suggest upregulation of cellular mechanisms protecting mitochondrial function in OA.

The chondrogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) has been used in the treatment and repair of cartilage defects; however, the in-depth regulatory mechanisms by which RNA modifications are involved in this process are still poorly understood. Here, we found that Sox9, a critical transcription factor that mediates chondrogenic differentiation, exhibited enhanced translation by ribosome sequencing in chondrogenic pellets, which was accompanied by increased 5-methylcytosine (m⁵C) and N6-methyladenosine (m⁶A) levels. Nsun4-mediated m⁵C and Mettl3-mediated m⁶A modifications were required for Sox9-regulated chondrogenic differentiation. Interestingly, we showed that in the 3’UTR of Sox9 mRNA, Nsun4 catalyzed the m⁵C modification and Mettl3 catalyzed the m⁶A modification. Furthermore, we found that Nsun4 and Mettl3 co-regulated the translational reprogramming of Sox9 via the formation of a complex. Surface plasmon resonance (SPR) assays showed that this complex was assembled along with the recruitment of Ythdf2 and eEF1α-1. Moreover, BMSCs overexpressing Mettl3 and Nsun4 can promote the repair of cartilage defects in vivo. Taken together, our study demonstrates that m⁵C and m⁶A co-regulate the translation of Sox9 during the chondrogenic differentiation of BMSCs, which provides a therapeutic target for clinical implications.

Nsun4-mediated m5C and Mettl3-mediated m6A are found to be required for Sox9-regulated chondrogenic differentiation, whereby Nsun4 and Mettl3 interact with each other and recruit Ythdf2 and eEF1a-1 to form a complex at the 3’UTR of Sox9.

Osteoarthritis (OA) is a progressive whole-joint disease; no disease-modifying drugs are currently available to stop or slow its process. Symptoms alleviation is the only treatment option. OA is the major cause of chronic pain in adults, with pain being the main symptom driving patients to seek medical help. OA pathophysiology is closely associated with the innate immune system, which is also closely linked to pain mediators leading to joint pain. Pain research has shown sex differences in the biology of pain, including sexually dimorphic responses from key cell types in the innate immune system. Not only is OA more prevalent in women than in men, but women patients also show worse OA outcomes, partially due to experiencing more pain symptoms despite having similar levels of structural damage. The cause of sex differences in OA and OA pain is poorly understood. This review provides an overview of the involvement of innate immunity in OA pain in joints and in the dorsal root ganglion. We summarize the emerging evidence of sex differences regarding innate immunity in OA pain. Our main goal with this review was to provide a scientific foundation for future research leading to alternative pain relief therapies targeting innate immunity that consider sex differences. This will ultimately lead to a more effective treatment of pain in both women and men.

• ReumaNederland

• extracellular matrix degradation
• lncRNA MEG3
• miR-93/TGFBR2
• osteoarthritis

Modern advances in molecular medicine have led to the reframing of osteoarthritis as a metabolically active, inflammatory disorder with local and systemic contributing factors. According to the ‘inflammatory theory’ of osteoarthritis, immune response to an initial damage is the key trigger that leads to progressive joint destruction. Several intertwined pathways are known to induce and govern articular inflammation, cartilage matrix degradation, and subchondral bone changes. Effective treatments capable of halting or delaying the progression of osteoarthritis remain elusive. As a result, supplements such as glucosamine and chondroitin sulphate are commonly used despite the lack of scientific consensus. A novel option for adjunctive therapy of osteoarthritis is LithoLexal^® Joint, a marine-derived, mineral-rich extract, that exhibited significant efficacy in clinical trials. LithoLexal^® has a lattice microstructure containing a combination of bioactive rare minerals. Mechanistic research suggests that this novel treatment possesses various potential disease-modifying properties, such as suppression of nuclear factor kappa-B, interleukin 1β, tumor necrosis factor α, and cyclooxygenase-2. Accordingly, LithoLexal^® Joint can be considered a disease-modifying adjunctive therapy (DMAT). LithoLexal^® Joint monotherapy in patients with knee osteoarthritis has significantly improved symptoms and walking ability with higher efficacy than glucosamine. Preliminary evidence also suggests that LithoLexal^® Joint may allow clinicians to reduce the dose of nonsteroidal anti-inflammatory drugs in osteoarthritic patients by up to 50%. In conclusion, the multi-mineral complex, LithoLexal^® Joint, appears to be a promising candidate for DMAT of osteoarthritis, which may narrow the existing gap in clinical practice.

• LithoLexal
• anti-inflammatory agents
• cytokine inhibitors
• disease-modifying adjunctive therapy
• lithothamnion
• osteoarthritis

Low vitamin D levels are associated with a more severe case of knee osteoarthritis (OA). However, there are few published reports concerning an association between vitamin D deficiency and functional status of individuals with OA and no reports about postural balance in this population.

To analyze the relationship between vitamin D deficiency and severity, functional status, and balance in elderly patients with OA.

In this cross-sectional study, 105 elderly patients with hip and knee OA were included. The severity was assessed by the Kellgren-Lawrence criteria. The functional status was assessed with the Lequesne index. Postural balance was assessed using a force platform, and center-of-pressure parameters (velocity at anteroposterior and mediolateral axis) were used as the balance outcomes. Serum 25(OH) vitamin D levels were measured using a chemiluminescence method.

Most of the patients (mean age: 70.6 ± 6.5 years) were female (n = 78, 74.3%). In the group with vitamin D deficiency, 43 patients (56.6%) had severe OA, while 33 patients (43.4%) had mild or moderate OA (χ² test, P = 0.04). Patients with vitamin D deficiency showed a higher Lequesne index score (Mann-Whitney test, P = 0.04), indicating a worse functional impairment when compared to individuals with normal vitamin D levels. Additionally, patients with vitamin D deficiency had worse postural balance according to the Mann-Whitney test (P = 0.03).

Vitamin D deficiency is associated with worse severity, functional status, and postural balance in patients with OA.

• Osteoarthritis
• Elderly
• Vitamin D
• Disability
• Severity
• Balance

Osteoarthritis (OA) is a global health issue with myriad pathophysiological factors and is one of the most common causes of chronic disability in adults due to pain and altered joint function.

Cite this article: EFORT Open Rev 2021;6:716-726. DOI: 10.1302/2058-5241.6.200040

• APS
• autologous protein solution
• joint preservation
• nSTRIDE
• orthobiologics
• osteoarthritis
• regenerative medicine

Previous research has identified N-myc downstream-regulated gene 2 (NDRG2) as one of the differentially expressed genes common to rat models of osteoarthritis (OA) and human OA. The purpose of this study was to investigate the role of NDRG2 in OA. In this study, an in vitro OA model was constructed by challenging ATDC5 chondrocytes with 10 ng/ml IL-1β. After transfection of pcDNA3.1(+)/NDRG2, qPCR and western blot were performed to assay NDRG2 expression. The analyses of cell viability, apoptosis and inflammatory molecule expression were employed respectively by CCK-8, TUNEL and ELISA. The protein expression related to apoptosis, inflammation or extracellular matrix (ECM) degradation was detected by western blot. The binding of Krüppel-like factor 5 (KLF5) to NDRG2 promoter was verified by means of dual-luciferase reporter assay. After overexpression of both NDRG2 and KLF5 in IL-1β-stimulated ATDC5 chondrocytes, corresponding assays were performed to examine cell viability, apoptosis, inflammatory response and ECM degradation. In ATDC5 chondrocytes challenged with IL-1β, NDRG2 expression was much lower than that in the control group, whereas it’s overexpression helped restored cell viability and reduce cell apoptosis, inflammatory response and ECM degradation. It was also observed that KLF5 expression was decreased in IL-1β-stimulated ATDC5 chondrocytes, and that KLF5 bound to the NDRG2 promoter. Importantly, overexpressing KLF5 could reverse the protective effect of NDRG2 overexpression on IL-1β-stimulated ATDC5. Overall, NDRG2 could be transcriptionally regulated by transcription factor KLF5 and may play a protective role against chondrocyte the inflammatory response and ECM degradation in OA.

• NDRG2
• Osteoarthritis
• chondrocyte apoptosis
• extracellular matrix degradation
• inflammatory response

• ADAMTS5
• Extracellular vesicles
• LPS-precondition
• Let-7b
• Osteoarthritis

• apolipoprotein J
• articular cartilage
• biomarker
• chondrocyte
• clusterin
• osteoarthritis (OA)
• proteomics
• secretome

• Casticin
• Chondrocyte
• Inflammation
• NF-κB
• Osteoarthritis
• Oxidative stress

Osteoarthritis is mainly caused by a degenerative joint disorder, which is characterized by the gradual degradation of articular cartilage and synovial inflammation. The chondrocyte, the unique resident cell type of articular cartilage, is crucial for the development of osteoarthritis. Previous studies revealed that P21-activated kinase-1 (PAK1) was responsible for the initiation of inflammation. The purpose of the present study was to determine the potential role of PAK1 in osteoarthritis. The level of PAK1 expression was measured by Western blot and quantitative real-time PCR in articular cartilage from osteoarthritis model rats and patients with osteoarthritis. In addition, the functional role of aberrant PAK1 expression was detected in the chondrocytes. We found that the expression of PAK1 was significantly increased in chondrocytes treated with osteoarthritis-related factors. Increased expression of PAK1 was also observed in knee articular cartilage samples from patients with osteoarthritis and osteoarthritis model rats. PAK1 was found to inhibit chondrocytes proliferation and to promote the production of inflammatory cytokines in cartilages chondrocytes. Furthermore, we found that PAK1 modulated the production of extracellular matrix and cartilage degrading enzymes in chondrocytes. Results of the present studies demonstrated that PAK1 might play an important role in the pathogenesis of osteoarthritis.

• Chondrocytes
• Osteoarthritis
• P21-activated Kinase-1
• Proliferation

Osteoarthritis (OA) is a progressive degenerative disease that manifests as pain and inflammation and often results in total joint replacement. There is significant interest in understanding how intra-articular injections made from autologous blood or bone marrow could alleviate symptoms and potentially intervene in the progression of the disease. There is in vitro an in vivo evidence that suggests that these therapies, including platelet-rich plasma (PRP), autologous anti-inflammatories (AAIs), and concentrated bone marrow aspirate (cBMA), can interrupt cartilage matrix degradation driven by pro-inflammatory cytokines. This review analyzes the evidence for and against inclusion of white blood cells, the potential role of platelets, and the less studied potential role of blood plasma when combining these components to create an autologous point-of-care therapy to treat OA. There has been significant focus on the differences between the various autologous therapies. However, evidence suggests that there may be more in common between groups and perhaps we should be thinking of these therapies on a spectrum of the same technology, each providing significant levels of anti-inflammatory cytokines that can be antagonists against the inflammatory cytokines driving OA symptoms and progression. While clinical data have demonstrated symptom alleviation, more studies will need to be conducted to determine whether these preclinical disease-modifying findings translate into clinical practice.

• autologous anti-inflammatory
• concentrated bone marrow aspirate
• intra-articular injection
• mechanism of action
• osteoarthritis
• platelet-rich plasma

• Anti-Inflammatory Agents/therapeutic use
• Humans
• Injections, Intra-Articular
• Knee Joint/immunology
• Knee Joint/pathology
• Osteoarthritis, Knee/immunology
• Osteoarthritis, Knee/pathology
• Osteoarthritis, Knee/therapy
• Platelet-Rich Plasma
• Point-of-Care Systems

• Biological
• Conservative
• Female
• Injection
• Joint preservation
• Knee
• Osteoarthritis
• Patellofemoral
• Therapy

Osteoarthritis (OA) is considered one of the most common arthritic diseases characterized by progressive degradation and abnormal remodeling of articular cartilage. Potential therapeutics for OA aim at restoring proper chondrocyte functioning and inhibiting apoptosis. Previous studies have demonstrated that tauroursodeoxycholic acid (TUDCA) showed anti-inflammatory and anti-apoptotic activity in many models of various diseases, acting mainly via alleviation of endoplasmic reticulum (ER) stress. However, little is known about cytoprotective effects of TUDCA on chondrocyte cells. The present study was designed to evaluate potential effects of TUDCA on interleukin-1β (IL-1β) and tunicamycin (TNC)-stimulated NHAC-kn chondrocytes cultured in normoxic and hypoxic conditions. Our results showed that TUDCA alleviated ER stress in TNC-treated chondrocytes, as demonstrated by reduced CHOP expression; however, it was not effective enough to prevent apoptosis of NHAC-kn cells in either normoxia nor hypoxia. However, co-treatment with TUDCA alleviated inflammatory response induced by IL-1β, as shown by down regulation of Il-1β, Il-6, Il-8 and Cox2, and increased the expression of antioxidant enzyme Sod2. Additionally, TUDCA enhanced Col IIα expression in IL-1β- and TNC-stimulated cells, but only in normoxic conditions. Altogether, these results suggest that although TUDCA may display chondoprotective potential in ER-stressed cells, further analyses are still necessary to fully confirm its possible recommendation as potential candidate in OA therapy.

• ER stress
• chondrocytes
• inflammation
• osteoarthritis
• tauroursodeoxycholate

Hip osteoarthritis (HOA) is characterized by degradation of the cartilage and synovitis. However, the pathohistological effects of synovial tissue inflammation on HOA are not clear. The aim of this study was to evaluate the expression of iNOS, BCL-2 and MMP-9 markers in different synovial cell populations. A total of 32 patients were evaluated retrospectively. Age, sex, height, weight, body mass index were recorded and lymphocyte, fibrocytes and macrophages were analysed in tissue sections. Osteoarthritis cartilage histopathology assessment system (OARSI), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Krenn score, Harris Hip Score (HHS) and Kellgren–Lawrence (K-L) grading of the hip joints were performed. Total hip arthroplasty was performed on 32 patients and controls. Patients were divided into two groups according to their disease severity. The tissues were immunohistochemically analysed. K-L grade and Krenn score differ between all three groups, but also between moderate and severe OA. Synovial lining cell layer, resident cells in stroma and especially inflammatory infiltration were increasing with severity of OA. iNOS expression in both intima and subintima was positively correlated with Krenn score in moderate and severe osteoarthritis (OA) groups. Expression of BCL-2 in intima of severe OA patients was positively correlated with Krenn score. In conclusion, iNOS, BCL-2 and MMP-9 are involved in the regulation of HOA. Our study indicates a relationship between the pathohistological features, the synovial inflammation and the cartilage condition at the time of hip replacement due to OA or femoral neck fracture.

• BCL-2
• Hip
• MMP-9
• cartilage
• iNOS
• osteoarthritis
• subchondral tissue
• synovia

• Aged
• Cross-Sectional Studies
• Female
• Gene Expression Regulation
• Genes, bcl-2
• Humans
• Male
• Matrix Metalloproteinase 9/biosynthesis
• Matrix Metalloproteinase 9/genetics
• Middle Aged
• Nitric Oxide Synthase Type II/biosynthesis
• Nitric Oxide Synthase Type II/genetics
• Osteoarthritis, Hip/metabolism
• Proto-Oncogene Proteins c-bcl-2/biosynthesis
• Synovial Membrane/metabolism
• Vascular Endothelial Growth Factor Receptor-1/analysis

• Articular cartilage
• Explant cultures
• Glucocorticoid
• Infrapatellar fat pad
• Methylprednisolone acetate
• Synovium

• bone marrow-derived mesenchymal stem cells
• cartilage
• inflammation
• miR-223
• osteoarthritis

This case-control study aims to examine the association between the Interleukin-6 (IL-6) rs12700386 polymorphism and the increased risk of developing osteoarthritis (OA) in the knee in the Chinese Han population.

We extracted DNA from 763 subjects (352 OA patients and 411 healthy controls). The relative expression levels of IL-6 in blood samples of patients with knee OA was determined by quantitative reverse transcription PCR (qRT-PCR) and polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was used for genotyping the IL-6 gene polymorphism.

We found that the IL-6 polymorphism rs12700386 enhanced patient susceptibility to developing knee OA. Based on a subgroup analysis, the risk of developing knee OA was elevated in smokers, drinkers, and subjects ≥55 years old or with BMI ≥ 25 kg/m². The combination of smoking, drinking, and having the rs12700386 genotype led to an increase in the risk of developing knee OA, indicating that an underlying interaction between gene and environment exists. The rs12700386 genotype was found to be correlated with an increase in IL-6 expression. We also found that IL-6 levels were significantly higher in the CC genotype compared to the GG genotype carriers in OA patients.

These data suggest that the rs12700386 polymorphism in the IL-6 gene leads to an increase in the risk of knee OA in Chinese Han individuals.

• Case-control study
• IL-6
• Osteoarthritis

• DEGs
• Inflammatory responses
• Natural product
• TNF-α cartilage

• Animals
• Anti-Inflammatory Agents/pharmacology
• Anti-Inflammatory Agents/therapeutic use
• Cell Survival/drug effects
• Cells, Cultured
• Chondrocytes/drug effects
• Chondrocytes/metabolism
• Inflammasomes/metabolism
• Knee Joint/drug effects
• Knee Joint/pathology
• Male
• NF-kappa B/metabolism
• NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
• Osteoarthritis/drug therapy
• Osteoarthritis/genetics
• Osteoarthritis/metabolism
• Osteoarthritis/pathology
• Rats, Sprague-Dawley
• Triterpenes/pharmacology
• Triterpenes/therapeutic use
• Tumor Necrosis Factor-alpha
• Ursolic Acid

• cartilage pathology
• chondral lesions
• gene therapy
• osteoarthritis

• Animals
• Cartilage, Articular/injuries
• Cartilage, Articular/pathology
• Genetic Therapy
• Humans
• Mice
• Osteoarthritis/genetics
• Osteoarthritis/pathology
• Osteoarthritis/therapy
• Rats
• Stem Cell Transplantation
• Tissue Engineering