- Email: [email protected]
MRI in OA research and the clinic
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Abstracts / Osteoarthritis and Cartilage 25 (2017) S1eS7
Results: We found that proliferative chondrocytes continued proliferation and did not undergo hypertrophy in Sik3 KO mouse embryos. Cartilage volume was larger in Sik3 KO mouse embryos. The activated form of SIK3 was highly expressed in degenerated cartilage from patients with osteoarthritis, but not so in normal cartilage. These results suggest that increased SIK3 activity is associated with osteoarthritis. In order to investigate how Sik3 affects the homeostasis of articular cartilage, we generated cartilage-specific Sik3 cKO mice in a tamoxifendependent manner. Tamoxifen administration abraded the Sik3 gene and increased the thickness of articular cartilage in Sik3 cKO mice. Sik3 cKO mice showed resistance to the development of DMM-induced osteoarthritis and decreased expression of type X collagen in the noncalcified zone of articular cartilage. These results suggest that Sik3 can be a target for drug development against osteoarthritis. We found the chemical compound pterosin B specifically inhibits Sik3 activity. Administration of pterosin B alleviated the development of osteoarthritis in DMM mice. Conclusions: Abrasion of Sik3 delayed chondrocyte hypertrophy and increased cartilage volume in embryonic epiphyseal cartilage and articular cartilage after birth in mice. Sik3 deletion conferred resistance to the development of osteoarthritis in mice, suggesting that Sik3 can be a target for treatment. Pterosin B, an inhibitor of Sik3, showed promise as a lead molecule for drug development. I-19 METABOLIC OA; DOES IT EXIST? D. Felson. Boston Univ., Boston, MA Purpose: There is strong evidence that local inflammation plays an important role in causing pain in osteoarthritis (OA) and in contributing to worsening structural deterioration of the affected joint. The metabolic syndrome, which increases the risk of heart disease, may influence OA by magnifying articular inflammation or may increase OA risk through other means. The metabolic syndrome consists of a combination of centralized obesity, elevated triglycerides, reduced HDL cholesterol, hypertension and elevated fasting blood sugar, all of which occur more often in obese persons. The purpose of this talk is to review and critically evaluate evidence on the association of metabolic syndrome and OA. Methods: Narrative review Results: A large number of epidemiologic studies have examined the relationship between metabolic syndrome and the occurrence of OA, especially in the knees. Findings from these studies are challenging to interpret. In general, when the studies have adjusted for obesity, a major risk factor for knee OA that confers increased mechanical load on knees, findings have not shown a consistent association of metabolic syndrome with knee OA. The association of obesity with an increased risk of hand OA has suggested that there is something about systemic adipose tissue accumulation that increases OA risk which might be related to metabolic syndrome. Studies examining the relationship of hand OA with metabolic syndrome have been more positive although not uniformly so. These will be reviewed. A high prevalence of hand OA has been reported in HIV-positive men with metabolic syndrome and this is strong evidence in favor of a relationship between metabolic syndrome and hand OA. A related question is whether any elements of the metabolic syndrome are particularly associated with the risk of OA rather than the metabolic syndrome itself. Initial studies suggested that central obesity may be uniquely related, with visceral fat being a major source of inflammatory adipokines. However the analytic approach to examining central obesity is challenging because central obesity and BMI are collinear and straightforward adjustment for BMI is probably not adequate to evaluate the effect of central obesity in causing OA. Several studies have suggested that hypertension is uniquely related to OA risk, and there is conflicting evidence regarding the relation of OA to diabetes. Conclusions: The evidence so far does not identify a clearcut association of metabolic syndrome with OA but is suggestive, especially for hand OA. Longitudinal studies are needed including those that focus on specific elements of metabolic syndrome and that explore biologically why elements of this syndrome might be related to OA risk.
I-20 CLINICAL TESTING IN VETERINARY OA P.D. Hanson. Ctr.xion Therapeutics, Baltimore, MD Premise: The conduct of clinical studies in dogs with naturally occurring osteoarthritis (OA) greatly augments work in animals with induced models. Background: The research and development of new analgesics to manage pain associated with OA in humans and animals typically involves use of induced OA or induced pain models in animals. These models may include use of Freund’s adjuvant, carrageenan, monoiodoacetate, urate crystals, surgical destabilization procedures or other methods in mice, rats, rabbits, guinea pigs, dogs, sheep, horses, and other species. These models may provide an efficacy signal but they also have limitations that vary by model and animal species used. Osteoarthritis occurs in 20% of adult pet dogs, generally, and 80% of dogs greater than 8 years of age. The pathophysiology of OA in dogs is similar to that in humans. Appropriately conducted clinical studies in pet dogs with naturally occurring OA offer greater relevance than induced models to the clinical condition in humans and dogs. This session will discuss clinical assessment of OA in pet dogs, including veterinarian examination, owner scales (eg, Client Specific Outcomes Measures [CSOM], Canine Brief Pain Inventory [CBPI], Liverpool Osteoarthritis in Dogs [LOAD], Glasgow Composite Measures Pain Scale and Short Form [GCMPS-SF], etc), and objective measures such as ground reaction forces and kinematics. Challenges, such as the caregiver placebo effect, also will be addressed. Regulatory requirements for the conduct of clinical trials in pet dogs will be discussed. Conclusion: Studies in dogs with naturally occurring OA can de-risk human development programs while providing parallel development of new therapeutics to manage OA pain in dogs. I-21 MRI IN OA RESEARCH AND THE CLINIC E. Oei. Erasmus MC, Univ. Med. Ctr., Rotterdam, Netherlands In this lecture current and emerging MRI methods for osteoarthritis (OA) will be reviewed, focusing on the knee joint. A distinction will be made between existing and clinically practical MRI techniques versus novel MRI methods that are still being used mostly as research tools. The recent insights regarding the “multi-tissue” involvement of OA will be highlighted along with the implications for MR imaging. Semiquantitative MRI scoring methods to systematically assess OA features in a variety of joint tissues are discussed, emphasizing the MRI osteoarthritis knee score (MOAKS). These scoring systems are mainly utilized for research purposes, but also provide a helpful template for clinical radiologists that can be applied on routine MRI of the knee. Among the tissue changes discussed are cartilage lesions, bone marrow lesions, synovitis, meniscal lesions, and miscellaneous soft tissue abnormalities that are believed to play a role in OA. Although most current guidelines do not recommend the use of MRI as a routine clinical examination for OA, awareness of relevant OA features may improve reporting of clinical MRI scans especially with the increasing number of MRI examinations being performed, also in older age groups. An overview of novel advanced MRI techniques for osteoarthritis is given, including quantitative techniques to assess tissue composition (delayed gadolinium-enhanced MRI of cartilage, T2- and T1rho mapping, GagCEST and sodium MRI), ultrashort echo time (UTE), PET-MRI and emerging methods to assess synovitis. Selected reported applications of these techniques in OA research will be presented. While these techniques hold promise because of their quantitative nature and improved sensitivity compared to existing methods, many of these will require more validation and technical improvements before they can be applied routinely OA research and the clinic. Take home points: - Osteoarthritis is currently considered a multi-tissue” or “whole organ” disease which affects many tissues in and around the joint. - Hence, MRI provides a more accurate and sensitive assessment of the processes involved in osteoarthritis than radiography, although conventional MRI methods are still looking at relatively advanced stages of osteoarthritis.
Abstracts / Osteoarthritis and Cartilage 25 (2017) S1eS7
- Although it is not indicated to perform MRI on a routine clinical basis to assess osteoarthritis, awareness of the MRI features of osteoarthritis could enhance the radiologist’s report of (knee) MRI in light of the increasing numbers of MRI performed in middle-aged patients. - Novel MR imaging techniques for osteoarthritis are promising, but need further optimization and validation before they can be implemented routinely in OA research and patient care. I-22 YEAR IN REVIEW e REHABILITATION AND OUTCOMES D. Schiphof, J.J. van den Driest, J. Runhaar. Erasmus MC, Rotterdam, Netherlands The purpose of this review is to highlight studies examining rehabilitation for osteoarthritis (OA) published between April 2016 and March 2017. We will conduct a systematic search of the literature including systematic reviews and randomized controlled trials investigating the effectiveness of rehabilitation interventions on pain and function. Key words in the search will include osteoarthritis; systematic review; randomized controlled trial. Inclusion criteria will be a systematic review or a randomized controlled trial, human OA patients, rehabilitation such as physiotherapy (physical therapy), exercise, bracing, lateral wedges, insoles, taping, acupuncture, combined therapies, electrotherapy, spa therapy, manual therapy, laser therapy, published in English. Excluded will be protocols for RCTs, abstracts without a full articles, conference proceedings, papers that replicated data from another article (secondary analyses from RCTs were eligible), oral or injectable medications, nutraceuticals and dietary weight loss (unless accompanied by exercise). This review will highlight a selection of studies based on their quality and perceived importance to the field including those that are innovative, inform the direction of the field or generate controversy. I-23 YEAR IN REVIEW e OSTEOARTHRITIS BIOLOGY T. Appleton. Western Univ., Canada, London, ON, Canada Purpose: To present highlights from the published literature on the biology of osteoarthritis (OA). A particular focus on pathophysiology of different OA phenotypes was made. Methods: A PubMed search was conducted in order to locate original research manuscripts published since the last OARSI meeting in 2016. Results: From review of the published literature, recent developments emerging as active areas of research over the past year include studies in the areas of OA-related pain sensitization particularly in animal models of OA, cartilage and chondrocyte physiology including autophagy, Wnt signaling, FGF signaling, and an emerging role for noncoding RNAs and epigenetics in the maintenance of homeostasis of multiple joint tissues. Once again, inflammation played a prominent role among studies in OA biology. Conclusions: Key findings and implications for potential future therapies are summarized and discussed. 1-24 YEAR IN REVIEW e CLINICAL A.E. Nelson. Univ. of North Carolina, Chapel Hill, NC Clinical research and epidemiologic studies in osteoarthritis over the past year will be discussed, utilizing articles identified through systematic review of the literature (using such terms as: osteoarthritis, epidemiology, treatment) from April 2016 to March 2017. I-25 YEAR IN REVIEW e GENETICS/GENOMICS AND EPIGENETICS M.J. Peffers. Univ. of Liverpool, Liverpool, United Kingdom The purpose of this review is to describe highlights from original research publications related to genetics, genomics and epigenetics with the intention of recognising significant advances. To identify relevant papers a Pubmed search was conducted for articles published between April 2016 and January 2017 using the search terms ‘osteoarthritis’ together with ‘genetics’, ‘genomics’, ‘epigenetics’, ‘microrna’, ‘lncRNA’, ‘DNA methylation’ and ‘histone modification’. The search term osteoarthritis generated almost 4000 references. Publications using the combination of descriptors osteoarthritis and genetics provided the most references (82 references). However this was reduced compared to the
S7
same period in the previous year; 8.1% to 2.1% (expressed as a percentage of the total publications combining the terms osteoarthritis and genetics). Publications combining the terms osteoarthritis with genomics (19 references), epigenetics (13 references), lncRNA (10 references), DNA methylation (18 references), histone modification (3 references) and microrna (50 references) were reviewed. There continues to be a year on year increase in publications researching microRNAs in osteoarthritis (expressed as a percentage of the total publications), with a doubling over the last 4 years. Selected studies chosen from the latest publications of high significance to osteoarthritis will be discussed. I-26 YEAR IN REVIEW e BIOMARKERS F.E. Watt. Kennedy Inst. of Rheumatology, Univ. of Oxford, Oxford, United Kingdom Purpose: To summarise important findings from biomarker studies relevant to osteoarthritis (OA), published from April 2016 to March 2017; to consider these findings in the context of new trends and technologies, and clinical and scientific need in OA. Methods: Studies were selected from a PubMed search conducted between 01/04/2016-01/03/2017. MeSH terms [biomarker] AND [osteoarthritis] were used; the search was restricted to English language and Full Text Available publications. Any biomarker was considered, including non-protein biomarkers: measurement of analytes in tissues or fluids relevant to OA pathogenesis and other clinical measurements which could represent novel biomarkers were also considered. Results: Studies were reviewed in 4 sub-groups: 1) An update on studies examining FNIH OA Biomarkers Consortium panel of biomarkers, particularly their ongoing application and qualification. Papers presenting control reference intervals, work on predictive validity and other longitudinal studies examining prognostic value of biomarkers in large cohorts are reviewed. 2) Novel studies measuring inflammatory biomarkers are overviewed, including complement, the performance of newer markers and studies in hand OA. 3) Non-protein based biomarkers, such as total/ mRNA, circulating non-coding RNAs, epigenetic markers and metabolomics; and 4) Discovery studies and those which illustrate new technologies or new multiplexing strategies are highlighted. Conclusions: Characterisation and qualification of various biomarkers is ongoing; several novel protein and non-protein candidate biomarkers have been reported this year. An ongoing desire to be able to stratify the disease arises from a real unmet clinical need to do so. Biomarkers may provide us with an opportunity to do this, via established panels or new discovery approaches employing array technology suited to large sample numbers. When focussing on OA, we should learn from related diseases and disciplines; large well-designed studies will enable us to maximise what biomarkers can tell us about underlying disease state and the potential for response to certain types of therapy. Biomarkers should not be considered in isolation; what they add to clinical measurements, imaging or other data either singly or as a group must be considered early. Consideration of novel types of biomarker, improving quality standards for sampling and testing across studies, and the ability to measure large numbers of molecules simultaneously in large cohorts and populations would all seem likely to bring about clinically applicable biomarkers, which are much needed in this disease. I-27 YEAR IN REVIEW - MECHANICS Y. Wang. Massachusetts Inst. of Technology, Cambridge, MA The purpose of this narrative review is to highlight recent advances on the topic of mechanics and mechanobiology of connective tissues in the synovial joint. A systematic literature review has been conducted using PubMed to identify research manuscripts published (or epub-online) between January 2016 to March 2017. The search terms osteoarthritis or cartilage AND mechanics or biomechanics or mechano produced 305 results. Overlapping themes in these manuscripts include clinical studies of gait and joint kinematics in response to mechanical damage/ interventions, new animal models of joint loading, mechanotransduction, and cell and matrix mechanics. Progress has also been made on understanding how biomechanical forces affect chondrocytes in normal cartilage and in engineered tissue. This review will also summarize recent advances in our understanding of the relationship between mechanical changes on the tissue, cellular, and molecular level and the progression of osteoarthritis.
Abstracts / Osteoarthritis and Cartilage 25 (2017) S1eS7
Results: We found that proliferative chondrocytes continued proliferation and did not undergo hypertrophy in Sik3 KO mouse embryos. Cartilage volume was larger in Sik3 KO mouse embryos. The activated form of SIK3 was highly expressed in degenerated cartilage from patients with osteoarthritis, but not so in normal cartilage. These results suggest that increased SIK3 activity is associated with osteoarthritis. In order to investigate how Sik3 affects the homeostasis of articular cartilage, we generated cartilage-specific Sik3 cKO mice in a tamoxifendependent manner. Tamoxifen administration abraded the Sik3 gene and increased the thickness of articular cartilage in Sik3 cKO mice. Sik3 cKO mice showed resistance to the development of DMM-induced osteoarthritis and decreased expression of type X collagen in the noncalcified zone of articular cartilage. These results suggest that Sik3 can be a target for drug development against osteoarthritis. We found the chemical compound pterosin B specifically inhibits Sik3 activity. Administration of pterosin B alleviated the development of osteoarthritis in DMM mice. Conclusions: Abrasion of Sik3 delayed chondrocyte hypertrophy and increased cartilage volume in embryonic epiphyseal cartilage and articular cartilage after birth in mice. Sik3 deletion conferred resistance to the development of osteoarthritis in mice, suggesting that Sik3 can be a target for treatment. Pterosin B, an inhibitor of Sik3, showed promise as a lead molecule for drug development. I-19 METABOLIC OA; DOES IT EXIST? D. Felson. Boston Univ., Boston, MA Purpose: There is strong evidence that local inflammation plays an important role in causing pain in osteoarthritis (OA) and in contributing to worsening structural deterioration of the affected joint. The metabolic syndrome, which increases the risk of heart disease, may influence OA by magnifying articular inflammation or may increase OA risk through other means. The metabolic syndrome consists of a combination of centralized obesity, elevated triglycerides, reduced HDL cholesterol, hypertension and elevated fasting blood sugar, all of which occur more often in obese persons. The purpose of this talk is to review and critically evaluate evidence on the association of metabolic syndrome and OA. Methods: Narrative review Results: A large number of epidemiologic studies have examined the relationship between metabolic syndrome and the occurrence of OA, especially in the knees. Findings from these studies are challenging to interpret. In general, when the studies have adjusted for obesity, a major risk factor for knee OA that confers increased mechanical load on knees, findings have not shown a consistent association of metabolic syndrome with knee OA. The association of obesity with an increased risk of hand OA has suggested that there is something about systemic adipose tissue accumulation that increases OA risk which might be related to metabolic syndrome. Studies examining the relationship of hand OA with metabolic syndrome have been more positive although not uniformly so. These will be reviewed. A high prevalence of hand OA has been reported in HIV-positive men with metabolic syndrome and this is strong evidence in favor of a relationship between metabolic syndrome and hand OA. A related question is whether any elements of the metabolic syndrome are particularly associated with the risk of OA rather than the metabolic syndrome itself. Initial studies suggested that central obesity may be uniquely related, with visceral fat being a major source of inflammatory adipokines. However the analytic approach to examining central obesity is challenging because central obesity and BMI are collinear and straightforward adjustment for BMI is probably not adequate to evaluate the effect of central obesity in causing OA. Several studies have suggested that hypertension is uniquely related to OA risk, and there is conflicting evidence regarding the relation of OA to diabetes. Conclusions: The evidence so far does not identify a clearcut association of metabolic syndrome with OA but is suggestive, especially for hand OA. Longitudinal studies are needed including those that focus on specific elements of metabolic syndrome and that explore biologically why elements of this syndrome might be related to OA risk.
I-20 CLINICAL TESTING IN VETERINARY OA P.D. Hanson. Ctr.xion Therapeutics, Baltimore, MD Premise: The conduct of clinical studies in dogs with naturally occurring osteoarthritis (OA) greatly augments work in animals with induced models. Background: The research and development of new analgesics to manage pain associated with OA in humans and animals typically involves use of induced OA or induced pain models in animals. These models may include use of Freund’s adjuvant, carrageenan, monoiodoacetate, urate crystals, surgical destabilization procedures or other methods in mice, rats, rabbits, guinea pigs, dogs, sheep, horses, and other species. These models may provide an efficacy signal but they also have limitations that vary by model and animal species used. Osteoarthritis occurs in 20% of adult pet dogs, generally, and 80% of dogs greater than 8 years of age. The pathophysiology of OA in dogs is similar to that in humans. Appropriately conducted clinical studies in pet dogs with naturally occurring OA offer greater relevance than induced models to the clinical condition in humans and dogs. This session will discuss clinical assessment of OA in pet dogs, including veterinarian examination, owner scales (eg, Client Specific Outcomes Measures [CSOM], Canine Brief Pain Inventory [CBPI], Liverpool Osteoarthritis in Dogs [LOAD], Glasgow Composite Measures Pain Scale and Short Form [GCMPS-SF], etc), and objective measures such as ground reaction forces and kinematics. Challenges, such as the caregiver placebo effect, also will be addressed. Regulatory requirements for the conduct of clinical trials in pet dogs will be discussed. Conclusion: Studies in dogs with naturally occurring OA can de-risk human development programs while providing parallel development of new therapeutics to manage OA pain in dogs. I-21 MRI IN OA RESEARCH AND THE CLINIC E. Oei. Erasmus MC, Univ. Med. Ctr., Rotterdam, Netherlands In this lecture current and emerging MRI methods for osteoarthritis (OA) will be reviewed, focusing on the knee joint. A distinction will be made between existing and clinically practical MRI techniques versus novel MRI methods that are still being used mostly as research tools. The recent insights regarding the “multi-tissue” involvement of OA will be highlighted along with the implications for MR imaging. Semiquantitative MRI scoring methods to systematically assess OA features in a variety of joint tissues are discussed, emphasizing the MRI osteoarthritis knee score (MOAKS). These scoring systems are mainly utilized for research purposes, but also provide a helpful template for clinical radiologists that can be applied on routine MRI of the knee. Among the tissue changes discussed are cartilage lesions, bone marrow lesions, synovitis, meniscal lesions, and miscellaneous soft tissue abnormalities that are believed to play a role in OA. Although most current guidelines do not recommend the use of MRI as a routine clinical examination for OA, awareness of relevant OA features may improve reporting of clinical MRI scans especially with the increasing number of MRI examinations being performed, also in older age groups. An overview of novel advanced MRI techniques for osteoarthritis is given, including quantitative techniques to assess tissue composition (delayed gadolinium-enhanced MRI of cartilage, T2- and T1rho mapping, GagCEST and sodium MRI), ultrashort echo time (UTE), PET-MRI and emerging methods to assess synovitis. Selected reported applications of these techniques in OA research will be presented. While these techniques hold promise because of their quantitative nature and improved sensitivity compared to existing methods, many of these will require more validation and technical improvements before they can be applied routinely OA research and the clinic. Take home points: - Osteoarthritis is currently considered a multi-tissue” or “whole organ” disease which affects many tissues in and around the joint. - Hence, MRI provides a more accurate and sensitive assessment of the processes involved in osteoarthritis than radiography, although conventional MRI methods are still looking at relatively advanced stages of osteoarthritis.
Abstracts / Osteoarthritis and Cartilage 25 (2017) S1eS7
- Although it is not indicated to perform MRI on a routine clinical basis to assess osteoarthritis, awareness of the MRI features of osteoarthritis could enhance the radiologist’s report of (knee) MRI in light of the increasing numbers of MRI performed in middle-aged patients. - Novel MR imaging techniques for osteoarthritis are promising, but need further optimization and validation before they can be implemented routinely in OA research and patient care. I-22 YEAR IN REVIEW e REHABILITATION AND OUTCOMES D. Schiphof, J.J. van den Driest, J. Runhaar. Erasmus MC, Rotterdam, Netherlands The purpose of this review is to highlight studies examining rehabilitation for osteoarthritis (OA) published between April 2016 and March 2017. We will conduct a systematic search of the literature including systematic reviews and randomized controlled trials investigating the effectiveness of rehabilitation interventions on pain and function. Key words in the search will include osteoarthritis; systematic review; randomized controlled trial. Inclusion criteria will be a systematic review or a randomized controlled trial, human OA patients, rehabilitation such as physiotherapy (physical therapy), exercise, bracing, lateral wedges, insoles, taping, acupuncture, combined therapies, electrotherapy, spa therapy, manual therapy, laser therapy, published in English. Excluded will be protocols for RCTs, abstracts without a full articles, conference proceedings, papers that replicated data from another article (secondary analyses from RCTs were eligible), oral or injectable medications, nutraceuticals and dietary weight loss (unless accompanied by exercise). This review will highlight a selection of studies based on their quality and perceived importance to the field including those that are innovative, inform the direction of the field or generate controversy. I-23 YEAR IN REVIEW e OSTEOARTHRITIS BIOLOGY T. Appleton. Western Univ., Canada, London, ON, Canada Purpose: To present highlights from the published literature on the biology of osteoarthritis (OA). A particular focus on pathophysiology of different OA phenotypes was made. Methods: A PubMed search was conducted in order to locate original research manuscripts published since the last OARSI meeting in 2016. Results: From review of the published literature, recent developments emerging as active areas of research over the past year include studies in the areas of OA-related pain sensitization particularly in animal models of OA, cartilage and chondrocyte physiology including autophagy, Wnt signaling, FGF signaling, and an emerging role for noncoding RNAs and epigenetics in the maintenance of homeostasis of multiple joint tissues. Once again, inflammation played a prominent role among studies in OA biology. Conclusions: Key findings and implications for potential future therapies are summarized and discussed. 1-24 YEAR IN REVIEW e CLINICAL A.E. Nelson. Univ. of North Carolina, Chapel Hill, NC Clinical research and epidemiologic studies in osteoarthritis over the past year will be discussed, utilizing articles identified through systematic review of the literature (using such terms as: osteoarthritis, epidemiology, treatment) from April 2016 to March 2017. I-25 YEAR IN REVIEW e GENETICS/GENOMICS AND EPIGENETICS M.J. Peffers. Univ. of Liverpool, Liverpool, United Kingdom The purpose of this review is to describe highlights from original research publications related to genetics, genomics and epigenetics with the intention of recognising significant advances. To identify relevant papers a Pubmed search was conducted for articles published between April 2016 and January 2017 using the search terms ‘osteoarthritis’ together with ‘genetics’, ‘genomics’, ‘epigenetics’, ‘microrna’, ‘lncRNA’, ‘DNA methylation’ and ‘histone modification’. The search term osteoarthritis generated almost 4000 references. Publications using the combination of descriptors osteoarthritis and genetics provided the most references (82 references). However this was reduced compared to the
S7
same period in the previous year; 8.1% to 2.1% (expressed as a percentage of the total publications combining the terms osteoarthritis and genetics). Publications combining the terms osteoarthritis with genomics (19 references), epigenetics (13 references), lncRNA (10 references), DNA methylation (18 references), histone modification (3 references) and microrna (50 references) were reviewed. There continues to be a year on year increase in publications researching microRNAs in osteoarthritis (expressed as a percentage of the total publications), with a doubling over the last 4 years. Selected studies chosen from the latest publications of high significance to osteoarthritis will be discussed. I-26 YEAR IN REVIEW e BIOMARKERS F.E. Watt. Kennedy Inst. of Rheumatology, Univ. of Oxford, Oxford, United Kingdom Purpose: To summarise important findings from biomarker studies relevant to osteoarthritis (OA), published from April 2016 to March 2017; to consider these findings in the context of new trends and technologies, and clinical and scientific need in OA. Methods: Studies were selected from a PubMed search conducted between 01/04/2016-01/03/2017. MeSH terms [biomarker] AND [osteoarthritis] were used; the search was restricted to English language and Full Text Available publications. Any biomarker was considered, including non-protein biomarkers: measurement of analytes in tissues or fluids relevant to OA pathogenesis and other clinical measurements which could represent novel biomarkers were also considered. Results: Studies were reviewed in 4 sub-groups: 1) An update on studies examining FNIH OA Biomarkers Consortium panel of biomarkers, particularly their ongoing application and qualification. Papers presenting control reference intervals, work on predictive validity and other longitudinal studies examining prognostic value of biomarkers in large cohorts are reviewed. 2) Novel studies measuring inflammatory biomarkers are overviewed, including complement, the performance of newer markers and studies in hand OA. 3) Non-protein based biomarkers, such as total/ mRNA, circulating non-coding RNAs, epigenetic markers and metabolomics; and 4) Discovery studies and those which illustrate new technologies or new multiplexing strategies are highlighted. Conclusions: Characterisation and qualification of various biomarkers is ongoing; several novel protein and non-protein candidate biomarkers have been reported this year. An ongoing desire to be able to stratify the disease arises from a real unmet clinical need to do so. Biomarkers may provide us with an opportunity to do this, via established panels or new discovery approaches employing array technology suited to large sample numbers. When focussing on OA, we should learn from related diseases and disciplines; large well-designed studies will enable us to maximise what biomarkers can tell us about underlying disease state and the potential for response to certain types of therapy. Biomarkers should not be considered in isolation; what they add to clinical measurements, imaging or other data either singly or as a group must be considered early. Consideration of novel types of biomarker, improving quality standards for sampling and testing across studies, and the ability to measure large numbers of molecules simultaneously in large cohorts and populations would all seem likely to bring about clinically applicable biomarkers, which are much needed in this disease. I-27 YEAR IN REVIEW - MECHANICS Y. Wang. Massachusetts Inst. of Technology, Cambridge, MA The purpose of this narrative review is to highlight recent advances on the topic of mechanics and mechanobiology of connective tissues in the synovial joint. A systematic literature review has been conducted using PubMed to identify research manuscripts published (or epub-online) between January 2016 to March 2017. The search terms osteoarthritis or cartilage AND mechanics or biomechanics or mechano produced 305 results. Overlapping themes in these manuscripts include clinical studies of gait and joint kinematics in response to mechanical damage/ interventions, new animal models of joint loading, mechanotransduction, and cell and matrix mechanics. Progress has also been made on understanding how biomechanical forces affect chondrocytes in normal cartilage and in engineered tissue. This review will also summarize recent advances in our understanding of the relationship between mechanical changes on the tissue, cellular, and molecular level and the progression of osteoarthritis.