Evolution and advancements in genomics and epigenomics in OA research: How far we have come.

OBJECTIVE: Osteoarthritis (OA) is the most prevalent musculoskeletal disease affecting articulating joint tissues, resulting in local and systemic changes that contribute to increased pain and reduced function. Diverse technological advancements have culminated in the advent of high throughput "omic" technologies, enabling identification of comprehensive changes in molecular mediators associated with the disease. Amongst these technologies, genomics and epigenomics - including methylomics and miRNomics, have emerged as important tools to aid our biological understanding of disease. DESIGN: In this narrative review, we selected articles discussing advancements and applications of these technologies to OA biology and pathology. We discuss how genomics, deoxyribonucleic acid (DNA) methylomics, and miRNomics have uncovered disease-related molecular markers in the local and systemic tissues or fluids of OA patients. RESULTS: Genomics investigations into the genetic links of OA, including using genome-wide association studies, have evolved to identify 100+ genetic susceptibility markers of OA. Epigenomic investigations of gene methylation status have identified the importance of methylation to OA-related catabolic gene expression. Furthermore, miRNomic studies have identified key microRNA signatures in various tissues and fluids related to OA disease. CONCLUSIONS: Sharing of standardized, well-annotated omic datasets in curated repositories will be key to enhancing statistical power to detect smaller and targetable changes in the biological signatures underlying OA pathogenesis. Additionally, continued technological developments and analysis methods, including using computational molecular and regulatory networks, are likely to facilitate improved detection of disease-relevant targets, in-turn, supporting precision medicine approaches and new treatment strategies for OA.

Three decades of advancements in osteoarthritis research: insights from transcriptomic, proteomic, and metabolomic studies.

OBJECTIVE: Osteoarthritis (OA) is a complex disease involving contributions from both local joint tissues and systemic sources. Patient characteristics, encompassing sociodemographic and clinical variables, are intricately linked with OA rendering its understanding challenging. Technological advancements have allowed for a comprehensive analysis of transcripts, proteomes and metabolomes in OA tissues/fluids through omic analyses. The objective of this review is to highlight the advancements achieved by omic studies in enhancing our understanding of OA pathogenesis over the last three decades. DESIGN: We conducted an extensive literature search focusing on transcriptomics, proteomics and metabolomics within the context of OA. Specifically, we explore how these technologies have identified individual transcripts, proteins, and metabolites, as well as distinctive endotype signatures from various body tissues or fluids of OA patients, including insights at the single-cell level, to advance our understanding of this highly complex disease. RESULTS: Omic studies reveal the description of numerous individual molecules and molecular patterns within OA-associated tissues and fluids. This includes the identification of specific cell (sub)types and associated pathways that contribute to disease mechanisms. However, there remains a necessity to further advance these technologies to delineate the spatial organization of cellular subtypes and molecular patterns within OA-afflicted tissues. CONCLUSIONS: Leveraging a multi-omics approach that integrates datasets from diverse molecular detection technologies, combined with patients' clinical and sociodemographic features, and molecular and regulatory networks, holds promise for identifying unique patient endophenotypes. This holistic approach can illuminate the heterogeneity among OA patients and, in turn, facilitate the development of tailored therapeutic interventions.

MicroRNAs as Prognostic Markers for Chondrogenic Differentiation Potential of Equine Mesenchymal Stromal Cells.

Mesenchymal stromal cells (MSCs) are a promising cell source for cartilage tissue regeneration in animals and humans but with large interdonor variation in their in vitro chondrogenic differentiation potential. Underlying molecular mechanisms responsible for culture-expanded MSC heterogeneity remain poorly understood. In this study, we sought to identify variations in microRNA (miRNA) signatures associated with cultured equine MSC chondrogenic differentiation potential from different donors. Neocartilage tissue generated from equine cord blood-derived MSCs was categorized as having either high or low chondrogenic potential (LCP) based on their histological appearance and quantification of glycosaminoglycan deposition. Using next-generation sequencing, we identified 30 differentially expressed miRNAs among undifferentiated MSC cultures that corresponded with their chondrogenic potential. Of note, MSCs with LCP upregulated miR-146a and miR-487b-3p, which was also observed by quantitative real-time polymerase chain reaction. Our findings suggest that miRNA profiling of equine MSC cultures may have prognostic value in selecting MSC donors with regard to their chondrogenic differentiation potential.

Characterization of miR-335-5p and miR-335-3p in human osteoarthritic tissues.

OBJECTIVE: We aimed to characterize the expression patterns, gene targets, and functional effects of miR-335-5p and miR-335-3p among seven primary human knee and hip osteoarthritic tissue types. METHODS: We collected synovial fluid, subchondral bone, articular cartilage, synovium, meniscus/labrum, infrapatellar/acetabular fat, anterior cruciate ligament/ligamentum teres, and vastus medialis oblique/quadratus femoris muscle (n = 7-20) from surgical patients with early- or late-stage osteoarthritis (OA) and quantified miR-335-5p and miR-335-3p expression by real-time PCR. Predicted gene targets were measured in knee OA infrapatellar fat following miRNA inhibitor transfection (n = 3), and prioritized gene targets were validated following miRNA inhibitor and mimic transfection (n = 6). Following pathway analyses, we performed Oil-Red-O staining to assess changes in total lipid content in infrapatellar fat. RESULTS: Showing a 227-fold increase in knee OA infrapatellar fat (the highest expressing tissue) versus meniscus (the lowest expressing tissue), miR-335-5p was more abundant than miR-335-3p (92-fold increase). MiR-335-5p showed higher expression across knee tissues versus hip tissues, and in late-stage versus early-stage knee OA fat. Exploring candidate genes, VCAM1 and MMP13 were identified as putative direct targets of miR-335-5p and miR-335-3p, respectively, showing downregulation with miRNA mimic transfection. Exploring candidate pathways, predicted miR-335-5p gene targets were enriched in a canonical adipogenesis network (p = 2.1e - 5). Modulation of miR-335-5p in late-stage knee OA fat showed an inverse relationship to total lipid content. CONCLUSION: Our data suggest both miR-335-5p and miR-335-3p regulate gene targets in late-stage knee OA infrapatellar fat, though miR-335-5p appears to be more prominent, with tissue-, joint-, and stage-specific effects.

Can genetics guide exercise prescriptions in osteoarthritis?

Osteoarthritis (OA) is the most common form of arthritis and has a multifactorial etiology. Current management for OA focuses on minimizing pain and functional loss, typically involving pharmacological, physical, psychosocial, and mind-body interventions. However, there remain challenges in determining which patients will benefit most from which interventions. Although exercise-based interventions are recommended as first-line treatments and are known to be beneficial for managing both the disease and illness of OA, the optimal exercise "prescription" is unknown, due in part to our limited understanding of the precise mechanisms underlying its action. Here we present our perspective on the potential role of genetics in guiding exercise prescription for persons with OA. We describe key publications in the areas of exercise and OA, genetics and OA, and exercise and genetics, and point to a paucity of knowledge at the intersection of exercise, genetics, and OA. We suggest there is emerging evidence to support the use of genetics and epigenetics to explain the beneficial effects of exercise for OA. We identify missing links in the existing research relating to exercise, genetics, and OA, and highlight epigenetics as a promising mechanism through which environmental exposures such as exercise may impact OA outcomes. We anticipate future studies will improve our understanding of how genetic and epigenetic factors mediate exercise-based interventions to support implementation and ultimately improve OA patient care.

Contribution of MicroRNA-27b-3p to Synovial Fibrotic Responses in Knee Osteoarthritis.

OBJECTIVE: Synovial fibrosis contributes to osteoarthritis (OA) pathology, but the underlying mechanisms remain unknown. We have observed increased microRNA-27b-3p (miR-27b-3p) levels in synovial fluid of patients with late-stage radiographic knee OA. Here, we investigated the contribution of miR-27b-3p to synovial fibrosis in patients with severe knee OA and in a mouse model of knee OA. METHODS: We stained synovium sections obtained from patients with radiographic knee OA scored according to the Kellgren/Lawrence scale and mice that underwent destabilization of the medial meniscus (DMM) for miR-27b-3p using in situ hybridization. We examined the effects of intraarticular injection of miR-27b-3p mimic into naive mouse knee joints and intraarticular injection of a miR-27b-3p inhibitor into mouse knee joints after DMM. We performed transfection with miR-27b-3p mimic and miR-27b-3p inhibitor in human OA fibroblast-like synoviocytes (FLS) using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) array, RNA sequencing, RT-qPCR, Western blotting, immunofluorescence, and migration assays. RESULTS: We observed increased miR-27b-3p expression in the synovium from patients with knee OA and in mice with DMM-induced arthritis. Injection of the miR-27b-3p mimic in mouse knee joints induced a synovial fibrosis-like phenotype, increased synovitis scores, and increased COL1A1 and α-smooth muscle actin (α-SMA) expression. In the mouse model of DMM-induced arthritis, injection of the miR-27b-3p inhibitor decreased α-SMA but did not change COL1A1 expression levels or synovitis scores. Transfection with the miR-27b-3p mimic in human OA FLS induced profibrotic responses, including increased migration and expression of key extracellular matrix (ECM) genes, but transfection with the miR-27b-3p inhibitor had the opposite effects. RNA sequencing identified a PPARG/ADAMTS8 signaling axis regulated by miR-27b-3p in OA FLS. Human OA FLS transfected with miR-27b-3p mimic and then treated with the PPARG agonist rosiglitazone or with ADAMTS8 small interfering RNA exhibited altered expression of select ECM genes. CONCLUSION: Our findings demonstrate that miR-27b-3p has a key role in ECM regulation associated with synovial fibrosis during OA.

Circulating microRNAs differentiate fast-progressing from slow-progressing and non-progressing knee osteoarthritis in the Osteoarthritis Initiative cohort.

Introduction: The objective of this study is to identify circulating microRNAs that distinguish fast-progressing radiographic knee osteoarthritis (OA) in the Osteoarthritis Initiative cohort by applying microRNA-sequencing. Methods: Participants with Kellgren-Lawrence (KL) grade 0/1 at baseline were included (N = 106). Fast-progressors were defined by an increase to KL 3/4 by 4-year follow-up (N = 20), whereas slow-progressors showed an increase to KL 2/3/4 only at 8-year follow-up (N = 35). Non-progressors remained at KL 0/1 by 8-year follow-up (N = 51). MicroRNA-sequencing was performed on plasma collected at baseline and 4-year follow-up from the same participants. Negative binomial models were fitted to identify differentially expressed (DE) microRNAs. Penalized logistic regression (PLR) analyses were performed to select combinations of DE microRNAs that distinguished fast-progressors. Area under the receiver operating characteristic curves (AUC) were constructed to evaluate predictive ability. Results: DE analyses revealed 48 microRNAs at baseline and 2 microRNAs at 4-year follow-up [false discovery rate (FDR) < 0.05] comparing fast-progressors with both slow-progressors and non-progressors. Among these were hsa-miR-320b, hsa-miR-320c, hsa-miR-320d, and hsa-miR-320e, which were predicted to target gene families, including members of the 14-3-3 gene family, involved in signal transduction. PLR models included miR-320 members as top predictors of fast-progressors and yielded AUC ranging from 82.6 to 91.9, representing good accuracy. Conclusion: The miR-320 family is associated with fast-progressing radiographic knee OA and merits further investigation as potential biomarkers and mechanistic drivers of knee OA.

A Network Biology Approach to Understanding the Tissue-Specific Roles of Non-Coding RNAs in Arthritis.

Discovery of non-coding RNAs continues to provide new insights into some of the key molecular drivers of musculoskeletal diseases. Among these, microRNAs have received widespread attention for their roles in osteoarthritis and rheumatoid arthritis. With evidence to suggest that long non-coding RNAs and circular RNAs function as competing endogenous RNAs to sponge microRNAs, the net effect on gene expression in specific disease contexts can be elusive. Studies to date have focused on elucidating individual long non-coding-microRNA-gene target axes and circular RNA-microRNA-gene target axes, with a paucity of data integrating experimentally validated effects of non-coding RNAs. To address this gap, we curated recent studies reporting non-coding RNA axes in chondrocytes from human osteoarthritis and in fibroblast-like synoviocytes from human rheumatoid arthritis. Using an integrative computational biology approach, we then combined the findings into cell- and disease-specific networks for in-depth interpretation. We highlight some challenges to data integration, including non-existent naming conventions and out-of-date databases for non-coding RNAs, and some successes exemplified by the International Molecular Exchange Consortium for protein interactions. In this perspective article, we suggest that data integration is a useful in silico approach for creating non-coding RNA networks in arthritis and prioritizing interactions for further in vitro and in vivo experimentation in translational research.

Tissue Collection and RNA Extraction from the Human Osteoarthritic Knee Joint.

Osteoarthritis (OA) is a chronic and degenerative joint disease most often affecting the knee. As there is currently no cure, total knee arthroplasty (TKA) is a common surgical intervention. Experiments using primary human OA tissues obtained from TKA provide the capability to investigate disease mechanisms ex vivo. While OA was previously thought to impact mainly the cartilage, it is now known to impact multiple tissues in the joint. This protocol describes patient selection, sample processing, tissue homogenization, RNA extraction, and quality control (based on RNA purity, integrity, and yield) from each of seven unique tissues to support disease mechanism investigation in the knee joint. With informed consent, samples were obtained from patients undergoing TKA for OA. Tissues were dissected, washed, and stored within 4 h of surgery by flash freezing for RNA or formalin fixation for histology. Collected tissues included articular cartilage, subchondral bone, meniscus, infrapatellar fat pad, anterior cruciate ligament, synovium, and vastus medialis oblique muscle. RNA extraction protocols were tested for each tissue type. The most significant modification involved the method of disintegration used for low-cell, high-matrix, hard tissues (considered as cartilage, bone, and meniscus) versus relatively high-cell, low-matrix, soft tissues (considered as fat pad, ligament, synovium, and muscle). It was found that pulverization was appropriate for hard tissues, and homogenization was appropriate for soft tissues. A proclivity for some subjects to yield higher RNA integrity number (RIN) values than other subjects consistently across multiple tissues was observed, suggesting that underlying factors such as disease severity may impact RNA quality. The ability to isolate high-quality RNA from primary human OA tissues provides a physiologically relevant model for sophisticated gene expression experiments, including sequencing, that can lead to clinical insights that are more readily translated to patients.

The future of deep phenotyping in osteoarthritis: How can high throughput omics technologies advance our understanding of the cellular and molecular taxonomy of the disease?

Osteoarthritis (OA) is the most common form of musculoskeletal disease with significant healthcare costs and unmet needs in terms of early diagnosis and treatment. Many of the drugs that have been developed to treat OA failed in phase 2 and phase 3 clinical trials or produced inconclusive and ambiguous results. High throughput omics technologies are a powerful tool to better understand the mechanisms of the development of OA and other arthritic diseases. In this paper we outline the strategic reasons for increasingly applying deep phenotyping in OA for the benefit of gaining a better understanding of disease mechanisms and developing targeted treatments. This editorial is intended to launch a special themed issue of Osteoarthritis and Cartilage Open addressing the timely topic of "Advances in omics technologies for deep phenotyping in osteoarthritis". High throughput omics technologies are increasingly being applied in mechanistic studies of OA and other arthritic diseases. Applying multi-omics approaches in OA is a high priority and will allow us to gather new information on disease pathogenesis at the cellular level, and integrate data from diverse omics technology platforms to enable deep phenotyping. We anticipate that new knowledge in this area will allow us to harness the power of Big Data Analytics and resolve the extremely complex and overlapping clinical phenotypes into molecular endotypes, revealing new information about the cellular taxonomy of OA and "druggable pathways", thus facilitating future drug development.

Applying the International Classification of Functioning, Disability and Health to understand osteoarthritis management in urban and rural community-dwelling seniors.

Objectives: The objectives of this study were to identify contextual factors as barriers or facilitators of osteoarthritis management in urban- and rural-dwelling seniors by applying the World Health Organization's International Classification of Functioning, Disability and Health (ICF). Design: Secondary analysis was performed on interview transcripts from urban- (n â€‹= â€‹11) and rural-dwelling (n â€‹= â€‹9) seniors living with osteoarthritis in Canada. Meaningful concepts were linked to ICF codes (Environmental Factors) according to established linking rules. Unclassified content (including Personal Factors) was subjected to qualitative content analysis. Results: A total of 481 and 410 meaningful concepts were identified in interview transcripts from urban and rural groups, respectively. For Environmental Factors, the majority of meaningful concepts linked to "Environmental Factors", then "Activities and Participation", and then "Body Functions" in the ICF. The most frequently linked codes were "e355 Health professionals", "e5801 Health systems", "e5800 Health services", and "e398 Support and relationships, other specified". The most salient barrier and facilitator to osteoarthritis management reflected in our results were "e5801 Health systems" and "e398 Support and relationships, other specified", respectively, for both urban and rural groups. For Personal Factors, qualitative content analysis of unclassified content revealed 3 key themes including (1) Coping Strategies; (2) Age of Osteoarthritis Diagnosis; and (3) Individual Circumstances. Conclusion: Beyond physical limitations, community-dwelling seniors with osteoarthritis encounter a wide range of biopsychosocial factors that can impact disease management. Applying the ICF, we identify "Environmental Factors" as a significant contextual factor impacting osteoarthritis management in both urban and rural communities.

A bioinformatics approach to microRNA-sequencing analysis.

The rapid expansion of Next Generation Sequencing (NGS) data availability has made exploration of appropriate bioinformatics analysis pipelines a timely issue. Since there are multiple tools and combinations thereof to analyze any dataset, there can be uncertainty in how to best perform an analysis in a robust and reproducible manner. This is especially true for newer omics applications, such as miRNomics, or microRNA-sequencing (miRNA-sequencing). As compared to transcriptomics, there have been far fewer miRNA-sequencing studies performed to date, and those that are reported seldom provide detailed description of the bioinformatics analysis, including aspects such as Unique Molecular Identifiers (UMIs). In this article, we attempt to fill the gap and help researchers understand their miRNA-sequencing data and its analysis. This article will specifically discuss a customizable miRNA bioinformatics pipeline that was developed using miRNA-sequencing datasets generated from human osteoarthritis plasma samples. We describe quality assessment of raw sequencing data files, reference-based alignment, counts generation for miRNA expression levels, and novel miRNA discovery. This report is expected to improve clarity and reproducibility of the bioinformatics portion of miRNA-sequencing analysis, applicable across any sample type, to promote sharing of detailed protocols in the NGS field.

Antisense oligonucleotide-based therapies for the treatment of osteoarthritis: Opportunities and roadblocks.

Osteoarthritis (OA) is a debilitating disease with no approved disease-modifying therapies. Among the challenges for developing treatment is achieving targeted drug delivery to affected joints. This has contributed to the failure of several drug candidates for the treatment of OA. Over the past 20 years, significant advances have been made in antisense oligonucleotide (ASO) technology for achieving targeted delivery to tissues and cells both in vitro and in vivo. Since ASOs are able to bind specific gene regions and regulate protein translation, they are useful for correcting aberrant endogenous mechanisms associated with certain diseases. ASOs can be delivered locally through intra-articular injection, and can enter cells through natural cellular uptake mechanisms. Despite this, ASOs have yet to be successfully tested in clinical trials for the treatment of OA. Recent chemical modification to ASOs have further improved cellular uptake and reduced toxicity. Among these are locked nucleic acid (LNA)-based ASOs, which have shown promising results in clinical trials for diseases such as hepatitis and dyslipidemia. Recently, LNA-based ASOs have been tested both in vitro and in vivo for their therapeutic potential in OA, and some have shown promising joint-protective effects in preclinical OA animal models. In order to accelerate the testing of ASO therapies in a clinical trial setting for OA, further investigation into delivery mechanisms is required. In this review article, we discuss opportunities for viral-, particle-, biomaterial-, and chemical modification-based therapies, which are currently in preclinical testing. We also address potential roadblocks in the clinical translation of ASO-based therapies for the treatment of OA, such as the limitations associated with OA animal models and the challenges with drug toxicity. Taken together, we review what is known and what would be useful to accelerate translation of ASO-based therapies for the treatment of OA.

Unique and overlapping GLI1 and GLI2 transcriptional targets in neoplastic chondrocytes.

Excessive Hedgehog (Hh) signaling in chondrocytes is sufficient to cause formation of enchondroma-like lesions which can progress to chondrosarcoma. To elucidate potential underlying mechanisms, we identified GLI1 and GLI2 target genes in human chondrosarcoma. Using chromatin immunoprecipitation (ChIP) sequencing and microarray data, in silico analyses were conducted to identify and characterize unique and overlapping GLI1 and GLI2 binding regions in neoplastic chondrocytes. After overlaying microarray data from human chondrosarcoma, 204 upregulated and 106 downregulated genes were identified as Hh-responsive Gli binding targets. After overlaying published Gli ChIP-on-chip data from mouse, 48 genes were identified as potential direct downstream targets of Hedgehog signaling with shared GLI binding regions in evolutionarily conserved DNA elements. Among these was BMP2, pointing to potential cross-talk between TGF beta signaling and Hh signaling. Our identification of potential target genes that are unique and common to GLI1 and GLI2 in neoplastic chondrocytes contributes to elucidating potential pathways through which Hh signaling impacts cartilage tumor biology.

microRNA-181a-5p antisense oligonucleotides attenuate osteoarthritis in facet and knee joints.

OBJECTIVES: We recently identified microRNA-181a-5p (miR-181a-5p) as a critical mediator involved in the destruction of lumbar facet joint (FJ) cartilage. In this study, we tested if locked nucleic acid (LNA) miR-181a-5p antisense oligonucleotides (ASO) could be used as a therapeutic to limit articular cartilage degeneration. METHODS: We used a variety of experimental models consisting of both human samples and animal models of FJ and knee osteoarthritis (OA) to test the effects of LNA-miR-181a-5p ASO on articular cartilage degeneration. Histopathological analysis including immunohistochemistry and in situ hybridisation were used to detect key OA catabolic markers and microRNA, respectively. Apoptotic/cell death markers were evaluated by flow cytometry. qPCR and immunoblotting were applied to quantify gene and protein expression. RESULTS: miR-181a-5p expression was increased in human FJ OA and knee OA cartilage as well as injury-induced FJ OA (rat) and trauma-induced knee OA (mouse) cartilage compared with control cartilage, correlating with classical OA catabolic markers in human, rat and mouse cartilage. We demonstrated that LNA-miR-181a-5p ASO in rat and mouse chondrocytes reduced the expression of cartilage catabolic and chondrocyte apoptotic/cell death markers in vitro. Treatment of OA-induced rat FJ or mouse knee joints with intra-articular injections of in vivo grade LNA-miR-181a-5p ASO attenuated cartilage destruction, and the expression of catabolic, hypertrophic, apoptotic/cell death and type II collagen breakdown markers. Finally, treatment of LNA-miR-181a-5p ASO in cultures of human knee OA chondrocytes (in vitro) and cartilage explants (ex vivo) further demonstrated its cartilage protective effects. CONCLUSIONS: Our data demonstrate, for the first time, that LNA-miR-181a-5p ASO exhibit cartilage-protective effects in FJ and knee OA.

Education and Social Support as Key Factors in Osteoarthritis Management Programs: A Scoping Review.

Systematic reviews of self-management programs for osteoarthritis suggest minimal evidence of benefit and indicate substantial heterogeneity in interventions. The purpose of this scoping review was to describe the nature of self-management interventions provided to patients with osteoarthritis focusing on the inclusion and type of education and social support components. We searched PsycINFO, EMBASE, MEDLINE, and Cochrane Library databases from 1990 to 2016 to identify studies addressing community-based management strategies for osteoarthritis that included aspects of disease-specific education and ongoing social support. Results are presented as a narrative synthesis to facilitate integration of diverse evidence. Data were extracted from 23 studies that met our inclusion and exclusion criteria, describing complex, multicomponent interventions for osteoarthritis. All studies included education components, and 18 of these were osteoarthritis-specific. Social support was most often offered through peers and health care professionals, but also through exercise trainers/instructors and researchers, and lasted between 5 and 52 weeks. We charted positive social interaction offered by peers in group settings and emotional/informational support offered by health care professionals. Overall, descriptions of self-management provided limited documentation of the rationale or content of the programs. This suggests that more precise definitions of the theoretical underpinnings, components, and mechanisms would be useful for greater insight into best practices for osteoarthritis self-management programs.

Patient perspectives on improving osteoarthritis management in urban and rural communities.

INTRODUCTION: Although there is no cure for osteoarthritis (OA), there are lifestyle modifications that can mitigate symptoms such as pain, and improve management of the disease. This information is not always translated to community-dwelling seniors. Individuals in rural areas often face additional challenges due to geographic isolation and decreased access to community services. METHODS: We used qualitative research methodology (hermeneutic phenomenology) to better understand the lived experiences of urban and rural community-dwelling seniors diagnosed with OA. We explored their sources of information about OA, how they manage their OA pain, and how OA management could be improved in the community. Purposeful sampling was used to recruit 20 information-rich participants (11 urban, 9 rural) in Ontario, Canada. All participants were aged >65 and diagnosed with OA. Semi-structured interviews were conducted, audio recorded, and transcribed verbatim. NVivo 11 Pro qualitative software was used to code transcripts. RESULTS: Thematic analysis revealed 9 key themes where 8 were common to urban and rural participants, and 1 was unique to rural participants. Most significant among the common themes was the description of the social network as a source of OA information, the trial-and-error approach used for OA management, and the individual contextualization of OA management. Our results suggest that there are several common experiences among urban- and rural-dwelling seniors living with OA, including the desire for support over time, but also a unique experience to rural-dwelling seniors, namely lack of access to local care. CONCLUSION: These findings can be used to improve translation of OA information in both urban and rural communities in Canada, highlighting that common strategies may be effective in different contexts for this disease.

Cultural Factors Influencing Osteoarthritis Care in Asian Communities: A Review of the Evidence.

With the prevalence of osteoarthritis (OA) increasing internationally, there is a need to study the impact of this disease on culturally diverse populations. Individuals of Asian descent make up more than 60% of the world population, yet comprehensive information on the cultural factors that impact OA care is not available. Scoping review methodology using directed content analysis was employed to identify and analyze existing research on OA care for Asians. A categorization matrix was developed using the six care areas from the OA clinical practice guidelines along with an additional three non-clinical areas (cross-cultural adaptation of clinical tools; psychological well-being; family systems and informal care) identified in an initial scan resulting in a total of nine OA care areas to guide initial coding. A full scoping review was conducted across five databases resulting in 656 abstracts screened. All text was coded using the categorization matrix and resulting subthemes were identified. A total of 74 articles were analyzed with 23 subthemes identified across the nine categories. Four new perspectives emerged to support OA care for Asian populations: (1) the importance of family and peer assistance, (2) the importance of culturally specific activities, (3) distrust in western medicine, and (4) impact of positive coping mechanisms on health appraisals. While Asians are more susceptible to knee and hand OA because of their cultural lifestyle factors (e.g. squatting for chores, hygiene and religious activities), and traditional beliefs on OA management (e.g. traditional diet, topical oils, physical therapy), many do not present themselves for conventional treatments (e.g. surgery) until all traditional treatments are exhausted. The results suggest that cultural factors influence the uptake of OA management practices among Asians. Greater awareness of these cultural factors may improve diagnosis, treatment, and management of OA among Asian patients.

Evaluating the design and reporting of pragmatic trials in osteoarthritis research.

Objectives: Among the challenges in health research is translating interventions from controlled experimental settings to clinical and community settings where chronic disease is managed daily. Pragmatic trials offer a method for testing interventions in real-world settings but are seldom used in OA research. The aim of this study was to evaluate the literature on pragmatic trials in OA research up to August 2016 in order to identify strengths and weaknesses in the design and reporting of these trials. Methods: We used established guidelines to assess the degree to which 61 OA studies complied with pragmatic trial design and reporting. We assessed design according to the pragmatic-explanatory continuum indicator summary and reporting according to the pragmatic trials extension of the CONsolidated Standards of Reporting Trials guidelines. Results: None of the pragmatic trials met all 11 criteria evaluated and most of the trials met between 5 and 8 of the criteria. Criteria most often unmet pertained to practitioner expertise (by requiring specialists) and criteria most often met pertained to primary outcome analysis (by using intention-to-treat analysis). Conclusion: Our results suggest a lack of highly pragmatic trials in OA research. We identify this as a point of opportunity to improve research translation, since optimizing the design and reporting of pragmatic trials can facilitate implementation of evidence-based interventions for OA care.