Osteoarthritis Phenotypes Research Articles

The role of leptin in the metabolic phenotype of osteoarthritis

The role of leptin in the metabolic phenotype of osteoarthritis

Synovial inflammation of osteoarthritis and rheumatoid arthritis revealed by single-cell and in silicodeconvolution bulk RNA sequencing

Purpose: Synovitis plays an important role in the pathogenesis of arthritis. Our objective was to differentiate the inflammatory phenotypes of osteoarthritis (OA) and rheumatoid arthritis (RA) synovium through single-cell RNA sequencing (scRNA-seq) and to test and validate the methodology by using bulk-RNA-seq data to create in silico scRNA-seq data for synovial tissue.

Effect of high-fat diet on integrated osteoarthritis phenotype-metabolome network in exercised mice

Purpose: Osteoarthritis (OA) - the main source of disability in US - is recognized as a whole-joint disease affecting cartilage, bone, synovium, intra-articular fat, muscle, and potentially other organ systems via factors released into the circulation. The interaction of local and systemic factors is a particular area of interest in OA phenotypes associated with obesity and metabolic syndrome. A better understanding of how local and systemic factors are interconnected and related to modifiable behaviors, such as physical activity, may provide new insight into OA biomarkers and treatment strategies.

TRPV1 alleviates osteoarthritis by inhibiting M1 macrophage polarization via CA2+/CAMKII/NRF2 signaling pathway

Purpose: To investigate the role and regulatory mechanism of transient receptor potential vanilloid 1 (TRPV1) in the M1 macrophage polarization and pathogenesis of osteoarthritis (OA). Methods: The levels of TRPV1 and macrophage markers (F4/80 and iNOS) were analyzed in the synovium of OA patients and in a rat OA model (radial transection of the medial meniscus) by immunofluorescence and immunohistochemical staining. The role of TRPV1 was examined using the rat OA model by intra-articular injection of capsaicin (CPS), a specific TRPV1 agonist. The levels of hyperplasia and cell infiltration of synovium, osteophyte formation and cartilage damage were assessed by a synovitis score, micro-CT and the Osteoarthritis Research Society International score, respectively. RAW264.7 cells were used to explore the mechanisms of M1 macrophage polarization by TRPV1. Results: TRPV1 expression and M1 macrophage infiltration were simultaneously increased in both human and rat OA synovium. More than 90% of the infiltrated M1 macrophages expressed TRPV1. The intra-articular injection of CPS significantly attenuated OA phenotypes, including joint swelling, synovitis, cartilage damage, and osteophyte formation. CPS treatment markedly reduced M1 macrophage infiltration in the synovium. TRPV1-evoked Ca2+ influx promoted the phosphorylation of calcium/calmodulin-dependent protein kinase II (CaMKII) and facilitated the nuclear localization of nuclear factor-erythroid 2-related factor 2 (Nrf2), which ultimately resulted in the inhibition of M1 macrophage polarization. Conclusions: TRPV1 attenuates the progression of OA by inhibiting M1 macrophage polarization in synovium via the Ca2+/CaMKII/Nrf2 signaling pathway. TRPV1 can be a therapeutic target for synovitis in OA

Modeling in vitro osteoarthritis phenotypes in a human vascularized bone construct based on a bone-marrow derived mesenchymal cell line and endothelial cells

Purpose: The main clinical indicators of osteoarthritis (OA) include loss of articular cartilage, altered subchondral bone remodeling, increased vascularization, and inflammation. Although cartilage degeneration has been always considered as the hallmark of OA, there is growing evidence that the subchondral bone and its associated vasculature could play an important role in OA onset. Reliable multi-cellular and complex human in vitro models are needed to resemble diverse tissues and to tackle different aspects of the pathology.

Clinical evaluation of thumb base osteoarthritis: A scoping review.

Thumb base osteoarthritis (OA) is a prevalent hand OA phenotype, associated with specific risk factors, treatment strategies, and requiring a distinct subset of evaluative approaches. This paper aimed at surveying our clinical evaluative methods and identifying gaps in our ability to capture the thumb's unique attributes and how they could impact our treatment recommendations. A scoping review was conducted in accordance with the Joanna Briggs Institute methodology to gather relevant published and non-published articles regarding clinical tests currently available to assess the physical presentation of thumb base OA with special consideration of its specific multifactorial parameters namely architecture, ligaments, biomechanics, neuromuscular control, and proprioception. A full search strategy of MEDLINE, CINAHL, EMBASE, Scopus, Google Scholar, and Clinical Trials.gov from their inception through May 2020 was performed. Of 1936 citation identified, 54 met the inclusion criteria. Fifty-two clinical physical tests for the evaluation of thumb base OA were extracted, most of which well suited to address research questions regarding efficacy of clinical intervention, however providing limited information regarding the underlying impairments of ligaments, biomechanics, neuromuscular or proprioceptive components. The tests and measures specific to the basal thumb OA phenotype, and capable of isolating its multifactorial contributors are scarce. Our limited physical assessment repertoire impedes our ability to describe and answer explicative research questions. Without these we cannot evaluate the effect of conservative management and provide specific treatment recommendations. Further research is needed to develop and validate distinct clinical tools for this debilitating pathology.

Discovery of bone morphogenetic protein 7-derived peptide sequences that attenuate the human osteoarthritic chondrocyte phenotype

Treatment of osteoarthritis (OA) is mainly symptomatic by alleviating pain to postpone total joint replacement. Bone morphogenetic protein 7 (BMP7) is a candidate morphogen for experimental OA treatment that favorably alters the chondrocyte and cartilage phenotype. Intra-articular delivery and sustained release of a recombinant growth factor for treating OA are challenging, whereas the use of peptide technology potentially circumvents many of these challenges. In this study, we screened a high-resolution BMP7 peptide library and discovered several overlapping peptide sequences from two regions in BMP7 with nanomolar bioactivity that attenuated the pathological OA chondrocyte phenotype. A single exposure of OA chondrocytes to peptides p[63−82] and p[113−132] ameliorated the OA chondrocyte phenotype for up to 8 days, and peptides were bioactive on chondrocytes in OA synovial fluid. Peptides p[63−82] and p[113−132] required NKX3-2 for their bioactivity on chondrocytes and provoke changes in SMAD signaling activity. The bioactivity of p[63−82] depended on specific evolutionary conserved sequence elements common to BMP family members. Intra-articular injection of a rat medial meniscal tear (MMT) model with peptide p[63−82] attenuated cartilage degeneration. Together, this study identified two regions in BMP7 from which bioactive peptides are able to attenuate the OA chondrocyte phenotype. These BMP7-derived peptides provide potential novel disease-modifying treatment options for OA.

Association between Oncostatin M Expression and Inflammatory Phenotype in Experimental Arthritis Models and Osteoarthritis Patients.

Pro-inflammatory cytokines are considered to play a major role in osteoarthritis (OA), yet so far, the specific cytokines involved in the pathology of OA have not been identified. Oncostatin M (OSM) is a cytokine from the interleukin 6 (IL-6) family that has been shown to be elevated in synovial fluid of most rheumatoid arthritis (RA) patients, but only in a limited subset of OA patients. Little is known about OSM in the different joint tissues during OA and how its expression correlates with hallmarks of disease. Here, we mapped OSM expression in the joint tissues of two rat models of arthritis: an acute inflammatory model and an instability-induced osteoarthritic model. OSM expression was correlated with hallmarks of OA, namely cartilage damage, synovitis, and osteophyte formation. Reanalysis of an existing dataset on cytokine profiling of OA synovial fluid was performed to assess pattern differences between patients positive and negative for OSM. In the inflammatory model, OSM expression correlated with synovitis and osteophyte formation but not with cartilage damage. On the contrary, in the instability model of OA, an increase in synovitis, cartilage damage, and osteophyte formation was observed without changes in OSM expression. In line with these findings, synovial fluid of OA patients with detectable OSM contained higher levels of other inflammatory cytokines, namely interferon gamma (IFN-γ), IL-1α and tumor necrosis factor alpha (TNF-α), likely indicating a more inflammatory state. Taken together these data indicate OSM might play a prominent role in inflammatory phenotypes of OA.

Prise en charge de l’arthrose du sujet très âgé

Osteoarthritis (OA) is one of the most disabling arthritic condition. Aging is a major risk factor and represent one of the three OA phenotypes currently identified, including mechanical or obesity-related osteoarthritis. In the very elderly, loss of function and pain due to osteoarthritis are primary concerns. Other conditions related to osteoarthritis are associated with aging, as malnutrition and sarcopenia. Management of osteoarthritis in the oldest old require a global evaluation and care. This evaluation emphasizes ethical concerns after a look at the cognitive impairment and functional disability, taking into account often-underestimated pain and stiffness. Assessment of muscular and nutritional parameters seem to be as important as the rheumatologic evaluation in this frail population. Symptomatic care is the best option in the impaired elderly whereas global care with a multidisciplinary approach is preferred in the frail population. Individualized decision making after global assessment is one of the specificities of the very elderly care because of the major risks of safety concerns, especially with pharmacological therapies.

The alteration of A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) in the knee joints of osteoarthritis mice

ABSTRACT The A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family is gradually being recognized as an important family of mediators that, along with the matrix metalloproteinases (MMPs), control the degradation process in osteoarthritis (OA). The objective of this study was to uncover the detailed alterations of ADAMTS1, ADAMTS2, and ADAMTS5 in the knee joint of OA mice. The OA model was established by anterior cruciate ligament transection (ACLT) on the knee joints of C57BL/6 J mice. The mice showed representative phenotypes of ACLT-induced OA, including obvious deterioration of the cartilage, reductions in the collagen and proteoglycan components in the cartilage matrix of OA mice, and increased inflammation and osteoclast activity. By qPCR, the gene expression levels of Adamts1, −2, and −5 were the top-ranked among Adamts1-5 in cartilage/chondrocytes, osteogenic tissue/osteoblasts, and cortical bone/osteocytes. Moreover, the protein expression levels of ADAMTS1, −2, and −5 were all increased in articular cartilage, the growth plate, and subchondral bone of the knee joint. The results suggest the important roles of ADAMTS1, −2, and −5 in OA disease, which will be helpful in further research on degenerative changes in OA.

An across-breed validation study of 46 genetic markers in canine hip dysplasia

BackgroundCanine hip dysplasia (CHD) is a common disease, with a complex genetic background. Dogs with severe CHD sometimes also suffer from osteoarthritis (OA), an inflammatory, often painful and incurable condition. Previous studies have reported breed-specific genetic loci associated with different hip dysplasia and OA phenotypes. However, the independent replication of the known associations within or across breeds has been difficult due to variable phenotype measures, inadequate sample sizes and the existence of population specific variants.ResultsWe execute a validation study of 46 genetic markers in a cohort of nearly 1600 dogs from ten different breeds. We categorize the dogs into cases and controls according to the hip scoring system defined by the Fédération Cynologique Internationale (FCI). We validate 21 different loci associated on fourteen chromosomes. Twenty of these associated with CHD in specific breeds, whereas one locus is unique to the across-breed study. We show that genes involved in the neddylation pathway are enriched among the genes in the validated loci. Neddylation contributes to many cellular functions including inflammation.ConclusionsOur study successfully replicates many loci and highlights the complex genetic architecture of CHD. Further characterisation of the associated loci could reveal CHD-relevant genes and pathways for improved understanding of the disease pathogenesis.

Mesenchymal stem cells genetically engineered to express platelet-derived growth factor and heme oxygenase-1 ameliorate osteoarthritis in a canine model

BackgroundMesenchymal stem cells (MSCs) are used for the treatment of osteoarthritis (OA), and MSC genetic engineering is expected to enhance cartilage repair. Here, we aimed to investigate the effect of MSCs overexpressing platelet-derived growth factor (PDGF) or heme oxygenase-1 (HO-1) in chondrocytes and synovial cells with an OA phenotype and assess the in vivo efficacy of intra-articular injections of these MSCs in canine OA models.MethodsCanine adipose-derived MSCs were transfected with canine PDGF (PDGF-MSCs) or HO-1 (HO-1-MSCs) using lentiviral vectors. Canine chondrocytes or synovial cells were stimulated with lipopolysaccharide (LPS) to mimic the inflammatory OA model and then co-cultured with MSCs, PDGF-MSCs, or HO-1-MSCs for 24 h and 72 h. The mRNA levels of pro-inflammatory, extracellular matrix-degradative/synthetic, or pain-related factors were measured after co-culture by real-time PCR. Furthermore, a surgery-induced canine OA model was established and the dogs were randomized into four groups: normal saline (n = 4), MSCs (n = 4), PDGF-MSCs (n = 4), and HO-1-MSCs (n = 4). The OA symptoms, radiographic OA severity, and serum matrix metallopeptidase (MMP)-13 levels were assessed before and 10 weeks after treatment, to evaluate the safety and efficacy of the modified MSCs.ResultsPDGF or HO-1 overexpression significantly reduced the expression of pro-inflammatory factors, MMP-13, and nerve growth factor elicited by LPS and increased that of aggrecan and collagen type 2 in chondrocytes (P < 0.05). In addition, the expression of aggrecanases was significantly downregulated in synovial cells, whereas that of tissue inhibitor of metalloproteinases was upregulated (P < 0.05). Furthermore, the co-cultured MSCs highly expressed genes that contributed to the maintenance of joint homeostasis (P < 0.05). In vivo studies showed that OA symptoms improved after administration of all MSCs. Also, PDGF-MSCs significantly improved limb function and reduced pain (P < 0.05). The results of the radiographic assessment and serum MMP-13 levels did not vary significantly compared to those of the control.ConclusionsGenetically modifying PDGF and HO-1 in MSCs is an effective strategy for treating OA, suggesting that PDGF-MSCs can be novel therapeutic agents for improving OA symptoms.

Moving toward targeting the right phenotype with the right platelet-rich plasma (PRP) formulation for knee osteoarthritis.

Intra-articular injections of platelet-rich plasma (PRP) and other novel blood-derived products developed specifically for osteoarthritis (OA) can provide pain relief and potential benefits in disease progression. Meta-analyses show the clinical superiority of PRP compared with other intra-articular injections, but results are modest and the effect sizes are small. PRP injections in knee OA are performed indiscriminately, but the clinical response varies enormously between patients because of an array of mixed OA phenotypes. Subgroup analyses are scarce; some studies stratify patients according to radiographic severity and found better results in early OA, without consensus for more advanced stages of the condition. Parallel identification of soluble and imaging biomarkers is essential to personalise and leverage PRP therapies. The inflammatory phenotype is most interesting from the PRP perspective because PRPs modulate inflammation by releasing a large pool of chemokines and cytokines, which interact with synovial fibroblasts and macrophages; in addition, they can modulate the innate immune response. No soluble biomarkers have been discovered that have implications for OA research and PRP interventions. Clinical examination of patients based on their inflammatory phenotype and imaging identification of pain sources and structural alterations could help discern who will respond to PRP. Synovial inflammation and bone marrow lesions are sources of pain, and intra-articular injections of PRP combined with subchondral bone injection can enhance clinical outcomes. Further refining ultrasound phenotypes may aid in personalising PRP therapies. Intra-articular delivery combined with injections in altered ligamentous structures, medial and coronal ligaments or premeniscal pes anserinus showed positive clinical outcomes. Although the evidence supporting these approaches are weak, they merit further consideration to refine PRP protocols and target the right OA phenotypes.

CircFAM160A2 Promotes Mitochondrial Stabilization and Apoptosis Reduction in Osteoarthritis Chondrocytes by Targeting miR-505-3p and SIRT3.

Competitive endogenous RNAs (ceRNAs), as a newly identified regulating mechanism, have been demonstrated to play a crucial role in various human diseases. An increasing number of recent studies have revealed that circular RNAs (circRNAs) can function as ceRNAs. However, little is known about the role of circFAM160A2 in the pathological process of osteoarthritis (OA). This study is the first to examine the crucial role of the circFAM160A2-miR-505-3p-SIRT3 axis in osteoarthritis progression. miR-505-3p was selected from the interaction of a microRNA (miRNA) microarray comparing chondrocytes in OA and normal conditions and prediction results from TargetScan. RT-qPCR was performed to assess the expression of circFAM160A2, miR-505-3p, and SIRT3. A dual luciferase assay was used to validate the binding of circFAM160A2, miR-505-3p, and SIRT3. We used lentivirus and adeno-associated virus to establish in vitro and in vivo overexpression models. Western blotting, apoptosis assay, ROS detection assay, Safranin O staining, and CCK-8 assay were employed to assess the role of circFAM160A2, miR-505-3p, and SIRT3. We found that miR-505-3p was upregulated and circFAM160A2 was downregulated in OA. While overexpression of circFAM160A2 decreased the production of extracellular matrix (ECM) degrading enzymes and ameliorated chondrocyte apoptosis and mitochondrial dysfunction, inhibition of miR-505-3p could reverse the protective effect of circFAM160A2 on the OA phenotype both in vitro and in vivo. In conclusion, circFAM160A2 can promote mitochondrial stabilization and apoptosis reduction in OA chondrocytes by targeting miR-505-3p and SIRT3, which might be a potential therapeutic target for OA therapy.

CircFAM160A2 Promotes Mitochondrial Stabilization and Apoptosis Reduction in Osteoarthritis Chondrocytes by Targeting miR-505-3p and SIRT3

Competitive endogenous RNAs (ceRNAs), as a newly identified regulating mechanism, have been demonstrated to play a crucial role in various human diseases. An increasing number of recent studies have revealed that circular RNAs (circRNAs) can function as ceRNAs. However, little is known about the role of circFAM160A2 in the pathological process of osteoarthritis (OA). This study is the first to examine the crucial role of the circFAM160A2-miR-505-3p-SIRT3 axis in osteoarthritis progression. miR-505-3p was selected from the interaction of a microRNA (miRNA) microarray comparing chondrocytes in OA and normal conditions and prediction results from TargetScan. RT-qPCR was performed to assess the expression of circFAM160A2, miR-505-3p , and SIRT3. A dual luciferase assay was used to validate the binding of circFAM160A2, miR-505-3p , and SIRT3. We used lentivirus and adeno-associated virus to establish in vitro and in vivo overexpression models. Western blotting, apoptosis assay, ROS detection assay, Safranin O staining , and CCK8 assay were employed to assess the role of circFAM160A2, miR-505-3p , and SIRT3. We found that miR-505-3p was upregulated and circFAM160A2 was downregulated in OA. While overexpression of circFAM160A2 decreased the production of extracellular matrix (ECM) degrading enzymes and ameliorated chondrocyte apoptosis and mitochondrial dysfunction, inhibition of miR-505-3p could reverse the protective effect of circFAM160A2 on the OA phenotype both in vitro and in vivo. In conclusion, circFAM160A2 can promote mitochondrial stabilization and apoptosis reduction in OA chondrocytes by targeting miR-505-3p and SIRT3, which might be a potential therapeutic target for OA therapy. Funding: This study was funded by National Natural Science Foundation of China (NO. 81401824, 81871793 and 81572173). Declaration of Interest: All authors have no conflicts of interest to declare. Ethical Approval: All animal experiments were approved by the Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine and carried out under the guidelines of the Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health.

Efficacy of phytotherapy and acupuncture in patients with metabolic phenotype of osteoarthritis: a pilot study

Efficacy of phytotherapy and acupuncture in patients with metabolic phenotype of osteoarthritis: a pilot study

Associations between the radiographic phenotypes and the presence of metabolic syndrome in patients with knee osteoarthritis.

We aimed to investigate the associations between the radiographic phenotypes and the presence of metabolic syndrome (MetS) in patients with knee osteoarthritis (OA). We evaluated women age 40 and over who presented to our outpatient clinics with knee pain and fulfilled the clinical and radiographic criteria for the classification of idiopathic OA of the knee. Patients were categorized into two groups concerning dominant radiographic phenotype. We included consecutive 50 patients in each group. All patients were evaluated in terms of MetS according to the revised diagnostic criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), as well as the World Health Organization (WHO). Overall, MetS prevalence was found to be 79% according to the NCEP ATP III-MetS criteria and 65% according to the WHOMetS criteria. Prevalence of MetS was higher in the joint space narrowing (JSN)-dominant group compared to the osteophyte (O)- dominant knee OA group, but the difference did not reach statistical significance. However, in subgroup analysis (54 patients) in which we excluded patients with a past medical history of type 2 diabetes mellitus (DM), the prevalence of NCEP ATP III-MetS was statistically significantly higher in the JSN-dominant group compared to the O-dominant group [22 (75.9%) vs. 12 (48%), respectively, p = 0.03]. Logistic regression analysis in the subgroup demonstrated that the presence of NCEP ATP III-MetS was an independent risk factor for JSN-dominant knee OA phenotype [OR and 95% CI = 3.48 (1.09-11.13)]. The prevalence of MetS is quite high in patients with knee OA and is particularly pronounced in patients with JSNdominant radiographic phenotype. Moreover, our results suggest that MetS is an independent risk factor for JSN-dominant knee OA in patients with no past medical history of DM.

Scénario général de l’arthrose

To date, there is no specific treatment for osteoarthritis (OA). The difficulty in developing a therapy that is effective both symptomatically and structurally is due first to the significant delay in diagnosis linked to the long asymptomatic period and to a largely radiographic definition, therefore not identifying the earliest stages. But this is also linked to the pathophysiological complexity of OA disease (or syndrome), involving all joint tissues, a complex cellular dialogue and many inflammatory and catabolic mediators. The initiating pathogenic mechanisms, often overcome at the time of diagnosis, depend at least in part on the OA phenotype. Four main phenotypes are now identified: metabolic, genetic, traumatic and age-related OA. After drawing the epidemiological and semiological outlines of OA pathology, we will try in this review to summarize the main pathophysiological mechanisms.

Determination of Pain Phenotypes in Knee Osteoarthritis Using Latent Profile Analysis.

To identify clinical phenotypes of knee osteoarthritis (OA) using measures from the following domains: 1) multimorbidity; 2) psychological distress; 3) pain sensitivity; and 4) knee impairment or pathology. Data were collected from 152 people with knee OA and from 31 pain-free individuals. In participants with knee OA, latent profile analysis (LPA) was applied to the following measures: normalized knee extensor strength, Functional Comorbidity Index (FCI), Pain Catastrophizing Scale (PCS), and local (knee) pressure pain threshold. Comparisons were performed between empirically derived phenotypes from the LPA and healthy older adults on these measures. Comparisons were also made between pheonotypes on pain intensity, functional measures, use of health care, and history of knee injury. LPA resulted in a four-group solution. Compared with all other groups, group 1 (9% of the study population) had higher FCI scores. Group 2 (63%) had elevated pain sensitivity and quadriceps weakness relative to group 4 and healthy older adults. Group 3 (11%) had higher PCS scores than all other groups. Group 4 (17%) had greater leg strength, except relative to healthy older adults, and reduced pain sensitivity relative to all groups. Groups 1 and 3 demonstrated higher pain and worse function than other groups, and group 4 had higher rates of knee injury. Four phenotypes of knee OA were identified using psychological factors, comorbidity status, pain sensitivity, and leg strength. Follow-up analyses supported the replicability of this phenotype structure, but future research is needed to determine its usefulness in knee OA care.

Fatty acid sensing GPCR (GPR84) signaling safeguards cartilage homeostasis and protects against osteoarthritis

It is well known that free fatty acids (FFAs) have beneficial effects on the skeletal system, however, which fatty acid sensing GPCR(s) and how the GPCR(s) regulating cartilage development and osteoarthritis (OA) pathogenesis is largely unknown. In this study, we found Gpr84, a receptor for medium-chain FFAs (MCFA), was the only FFA-sensing GPCR in human and mouse chondrocytes that exhibited elevated expression when stimulated by interleukin (IL)-1β. Gpr84-deficiency upregulated cartilage catabolic regulator expression and downregulated anabolic factor expression in the IL-1β-induced cell model and the destabilization of the medial meniscus (DMM)-induced OA mouse model. Gpr84−/− mice exhibited an aggravated OA phenotype characterized by severe cartilage degradation, osteophyte formation and subchondral bone sclerosis. Moreover, activating Gpr84 directly enhanced cartilage extracellular matrix (ECM) generation while knockout of Gpr84 suppressed ECM-related gene expression. Especially, the agonists of GPR84 protected human OA cartilage explants against degeneration by inducing cartilage anabolic factor expression. At the molecular level, GPR84 activation inhibited IL-1β-induced NF-κB signaling pathway. Furthermore, deletion of Gpr84 had little effect on articular and spine cartilaginous tissues during skeletal growth. Together, all of our results demonstrated that fatty acid sensing GPCR (Gpr84) signaling played a critical role in OA pathogenesis, and activation of GPR84 or MCFA supplementation has potential in preventing the pathogenesis and progression of OA without severe cartilaginous side effect.