Browsing by Subject "KNEE OSTEOARTHRITIS"

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  • Kringel, D.; Lippmann, C.; Parnham, M. J.; Kalso, E.; Ultsch, A.; Lötsch, J. (2018)
    Background Human genetic research has implicated functional variants of more than one hundred genes in the modulation of persisting pain. Artificial intelligence and machine-learning techniques may combine this knowledge with results of genetic research gathered in any context, which permits the identification of the key biological processes involved in chronic sensitization to pain. MethodsResultsBased on published evidence, a set of 110 genes carrying variants reported to be associated with modulation of the clinical phenotype of persisting pain in eight different clinical settings was submitted to unsupervised machine-learning aimed at functional clustering. Subsequently, a mathematically supported subset of genes, comprising those most consistently involved in persisting pain, was analysed by means of computational functional genomics in the Gene Ontology knowledgebase. Clustering of genes with evidence for a modulation of persisting pain elucidated a functionally heterogeneous set. The situation cleared when the focus was narrowed to a genetic modulation consistently observed throughout several clinical settings. On this basis, two groups of biological processes, the immune system and nitric oxide signalling, emerged as major players in sensitization to persisting pain, which is biologically highly plausible and in agreement with other lines of pain research. ConclusionsSignificanceThe present computational functional genomics-based approach provided a computational systems-biology perspective on chronic sensitization to pain. Human genetic control of persisting pain points to the immune system as a source of potential future targets for drugs directed against persisting pain. Contemporary machine-learned methods provide innovative approaches to knowledge discovery from previous evidence. We show that knowledge discovery in genetic databases and contemporary machine-learned techniques can identify relevant biological processes involved in Persitent pain.
  • Niemelä, Tytti M.; Tulamo, Riitta-Mari; Hielm-Björkman, Anna K. (2016)
    Background: Intra-articular inflammation resulting in lameness is a common health problem in horses. Exogenous intra-articular hyaluronic acid has been shown to provide an analgesic effect and reduce pain in equine and human osteoarthritis. High molecular weight non-animal stabilized hyaluronic acid (NASHA) has gained popularity in the treatment of human arthritic conditions due to its long-acting pain-relieving effects. The aim of this study was to compare the response to treatment of lameness localized in the equine metacarpophalangeal joint injected with non-animal stabilized hyaluronic acid (NASHA) and placebo (saline). Twenty-seven clinically lame horses with a positive response to diagnostic intra-articular anaesthesia of the metacarpophalangeal joint and with no, or at most mild, radiographic changes in this joint were included in the study. Horses in the treatment group (n = 14) received 3 mL of a NASHA product intra-articularly, and those in the placebo group (n = 13) received an equivalent volume of sterile 0.9 % saline solution. Results: The change in the lameness score did not significantly differ between NASHA and placebo groups (P = 0.94). Scores in the flexion test improved more in the NASHA group compared with placebo (P = 0.01). The changes in effusion and pain in flexion were similar (P = 0.94 and P = 0.27, respectively) when NASHA and placebo groups were compared. A telephone interview follow-up of the owners three months post-treatment revealed that 14 of the 21 horses (67 %) were able to perform at their previous level of exercise. Conclusions: In the present study, a single IA NASHA injection was not better than a single saline injection for reducing lameness in horses with synovitis or mild osteoarthritis. However, the results of this study indicate that IA NASHA may have some beneficial effects in modifying mild clinical signs but more research is needed to evaluate whether the positive effect documented ie. reduced response in the flexion test is a true treatment effect.
  • Näkki, Annu; Kouhia, Sanna T.; Saarela, Janna; Harilainen, Arsi; Tallroth, Kaj; Videman, Tapio; Battie, Michele C.; Kaprio, Jaakko; Peltonen, Leena; Kujala, Urho M. (2010)
    BACKGROUND: In search for genes predisposing to osteoarthritis (OA), several genome wide scans have provided evidence for linkage on 2q. In this study we targeted a 470 kb region on 2q11.2 presenting the locus with most evidence for linkage to severe OA of distal interphalangeal joints (DIP) in our genome wide scan families. METHODS: We genotyped 32 single nucleotide polymorphisms (SNPs) in this 470 kb region comprising six genes belonging to the interleukin 1 superfamily and monitored for association with individual SNPs and SNP haplotypes among severe familial hand OA cases (material extended from our previous linkage study; n = 134), unrelated end-stage bilateral primary knee OA cases (n = 113), and population based controls (n = 436). RESULTS: Four SNPs in the IL1R1 gene, mapping to a 125 kb LD block, provided evidence for association with hand OA in family-based and case-control analysis, the strongest association being with SNP rs2287047 (p-value = 0.0009). CONCLUSIONS: This study demonstrates an association between severe hand OA and IL1R1 gene. This gene represents a highly relevant biological candidate since it encodes protein that is a known modulator of inflammatory processes associated with joint destruction and resides within a locus providing consistent evidence for linkage to hand OA. As the observed association did not fully explain the linkage obtained in the previous study, it is plausible that also other variants in this genome region predispose to hand OA.
  • Mustonen, Anne-Mari; Käkelä, Reijo; Finnilä, Mikko A. J.; Sawatsky, Andrew; Korhonen, Rami K.; Saarakkala, Simo; Herzog, Walter; Paakkonen, Tommi; Nieminen, Petteri (2019)
    The infrapatellar fat pad (IFP) of the knee joint has received lots of attention recently due to its emerging role in the pathogenesis of osteoarthritis (OA), where it displays an inflammatory phenotype. The aim of the present study was to examine the infrapatellar fatty acid (FA) composition in a rabbit (Oryctolagus cuniculus) model of early OA created by anterior cruciate ligament transection (ACLT).
  • FIDELITY Finnish Degenerative Meni; Sihvonen, Raine; Paavola, Mika; Malmivaara, Antti; Itälä, Ari; Joukainen, Antti; Kalske, Juha; Nurmi, Heikki; Kumm, Jaanika; Sillanpää, Niko; Kiekara, Tommi; Turkiewicz, Aleksandra; Toivonen, Pirjo; Englund, Martin; Taimela, Simo; Järvinen, Teppo L. N. (2020)
    Objectives To assess the long-term effects of arthroscopic partial meniscectomy (APM) on the development of radiographic knee osteoarthritis, and on knee symptoms and function, at 5 years follow-up. Design Multicentre, randomised, participant- and outcome assessor-blinded, placebo-surgery controlled trial. Setting Orthopaedic departments in five public hospitals in Finland. Participants 146 adults, mean age 52 years (range 35-65 years), with knee symptoms consistent with degenerative medial meniscus tear verified by MRI scan and arthroscopically, and no clinical signs of knee osteoarthritis were randomised. Interventions APM or placebo surgery (diagnostic knee arthroscopy). Main outcome measures We used two indices of radiographic knee osteoarthritis (increase in Kellgren and Lawrence grade >= 1, and increase in Osteoarthritis Research Society International (OARSI) atlas radiographic joint space narrowing and osteophyte sum score, respectively), and three validated patient-relevant measures of knee symptoms and function ( Western Ontario Meniscal Evaluation Tool (WOMET), Lysholm, and knee pain after exercise using a numerical rating scale). Results There was a consistent, slightly greater risk for progression of radiographic knee osteoarthritis in the APM group as compared with the placebo surgery group (adjusted absolute risk difference in increase in Kellgren-Lawrence grade >= 1 of 13%, 95% CI -2% to 28%; adjusted absolute mean difference in OARSI sum score 0.7, 95% CI 0.1 to 1.3). There were no relevant between-group differences in the three patient-reported outcomes: adjusted absolute mean differences (APM vs placebo surgery), -1.7 (95% CI -7.7 to 4.3) in WOMET, -2.1 (95% CI -6.8 to 2.6) in Lysholm knee score, and -0.04 (95% CI -0.81 to 0.72) in knee pain after exercise, respectively. The corresponding adjusted absolute risk difference in the presence of mechanical symptoms was 18% (95% CI 5% to 31%); there were more symptoms reported in the APM group. All other secondary outcomes comparisons were similar. Conclusions APM was associated with a slightly increased risk of developing radiographic knee osteoarthritis and no concomitant benefit in patient-relevant outcomes, at 5 years after surgery.
  • Sihvonen, Raine; Paavola, Mika; Malmivaara, Antti; Itälä, Ari; Joukainen, Antti; Nurmi, Heikki; Kalske, Juha; Ikonen, Anna; Järvelä, Timo; Järvinen, Tero A. H.; Kanto, Kari; Karhunen, Janne; Knifsund, Jani; Kröger, Heikki; Kääriäinen, Tommi; Lehtinen, Janne; Nyrhinen, Jukka; Paloneva, Juha; Päiväniemi, Outi; Raivio, Marko; Sahlman, Janne; Sarvilinna, Roope; Tukiainen, Sikri; Välimäki, Ville-Valtteri; Äärimaa, Ville; Toivonen, Pirjo; Järvinen, Teppo L. N.; FIDELITY Finnish Degenerative (2018)
    Objective To assess if arthroscopic partial meniscectomy (APM) is superior to placebo surgery in the treatment of patients with degenerative tear of the medial meniscus. Methods In this multicentre, randomised, participant-blinded and outcome assessor-blinded, placebo-surgery controlled trial, 146 adults, aged 35-65 years, with knee symptoms consistent with degenerative medial meniscus tear and no knee osteoarthritis were randomised to APM or placebo surgery. The primary outcome was the between-group difference in the change from baseline in the Western Ontario Meniscal Evaluation Tool (WOMET) and Lysholm knee scores and knee pain after exercise at 24 months after surgery. Secondary outcomes included the frequency of unblinding of the treatment-group allocation, participants' satisfaction, impression of change, return to normal activities, the incidence of serious adverse events and the presence of meniscal symptoms in clinical examination. Two subgroup analyses, assessing the outcome on those with mechanical symptoms and those with unstable meniscus tears, were also carried out. Results In the intention-to-treat analysis, there were no significant between-group differences in the mean changes from baseline to 24 months in WOMET score: 27.3 in the APM group as compared with 31.6 in the placebo-surgery group (between-group difference, -4.3; 95% CI, -11.3 to 2.6); Lysholm knee score: 23.1 and 26.3, respectively (-3.2; -8.9 to 2.4) or knee pain after exercise, 3.5 and 3.9, respectively (-0.4; -1.3 to 0.5). There were no statistically significant differences between the two groups in any of the secondary outcomes or within the analysed subgroups. Conclusions In this 2-year follow-up of patients without knee osteoarthritis but with symptoms of a degenerative medial meniscus tear, the outcomes after APM were no better than those after placebo surgery. No evidence could be found to support the prevailing ideas that patients with presence of mechanical symptoms or certain meniscus tear characteristics or those who have failed initial conservative treatment are more likely to benefit from APM.
  • Heikkilä, Helka M.; Jokinen, Tarja S.; Syrjä, Pernilla; Junnila, Jouni; Hielm-Björkman, Anna; Laitinen-Vapaavuori, Outi (2018)
    Objective To investigate the clinical, cytological, and histopathological adverse effects of intra-articularly injected botulinum toxin A in dogs and to study whether the toxin spreads from the joint after the injection. Methods A longitudinal, placebo-controlled, randomized clinical trial was conducted with six healthy laboratory Beagle dogs. Stifle joints were randomized to receive either 30 IU of onabotulinum toxin A or placebo in a 1: 1 ratio. Adverse effects and spread of the toxin were examined by evaluating dynamic and static weight-bearing of the injected limbs, by assessing painless range of motion and pain on palpation of joints, and by performing synovial fluid analysis, neurological examination, and electrophysiological recordings at different examination timepoints in a 12-week period after the injections. The dogs were then euthanized and autopsy and histopathological examination of joint structures and adjacent muscles and nerves were performed. Results Intra-articular botulinum toxin A did not cause local weakness or injection site pain. Instead, static weight-bearing and painless range of motion of stifle joints decreased in the placebo limbs. No clinically significant abnormalities associated with intra-articular botulinum toxin A were detected in the neurological examinations. Electrophysiological recordings showed low compound muscle action potentials in two dogs in the botulinum toxin A-injected limb. No significant changes were detected in the synovial fluid. Autopsy and histopathological examination of the joint and adjacent muscles and nerves did not reveal histopathological adverse effects of the toxin. Conclusion Intra-articular botulinum toxin A does not produce significant clinical, cytological, or histopathological adverse effects in healthy dogs. Based on the electrophysiological recordings, the toxin may spread from the joint, but its clinical impact seems to be low.
  • Nakki, Annu; Rodriguez-Fontenla, Cristina; Gonzalez, Antonio; Harilainen, Arsi; Leino-Arjas, Paivi; Heliovaara, Markku; Eriksson, Johan G.; Tallroth, Kaj; Videman, Tapio; Kaprio, Jaakko; Saarela, Janna; Kujala, Urho M. (2016)
    Objectives: Osteoarthritis (OA) is a joint disease common in the elderly. There is a prior functional evidence for different matrix metalloproteinases (MMPs), such as MMP8 and MMP9, having a role in the breakdown of cartilage extracellular matrix in OA. Thus, we analyzed whether the common genetic variants of MMP8 and MMP9 contribute to the risk of OA. Materials and methods: In total, 13 common tagging single-nucleotide polymorphisms (SNPs) were studied in a discovery knee OA cohort of 185 cases and 895 controls. For validation, two knee OA replication cohorts and two hand OA replication cohorts were studied (altogether 1369 OA cases, 4445 controls in the five cohorts). The chi(2) test for individual study cohorts and Cochran-Mantel-Haenszel test for combined meta-analysis were calculated using Plink. Results: The rs1940475 SNP in MMP8 showed suggestive association in the discovery cohort (OR = 0.721, 95% CI 0.575-0.906; p = 0.005). Other knee and hand OA replication study cohorts showed similar trend for the predisposing allele without reaching statistical significance in independent replication cohorts nor in their meta-analysis (p > 0.05). Meta-analysis of all five hand and knee OA study cohorts yielded a p-value of 0.027 (OR = 0.904, 95% CI 0.826-0.989). Conclusions: Initial analysis of the MMP8 gene showed suggestive association between rs1940475 and knee OA, but the finding did not replicate in other study cohorts, even though the trend for predisposing allele was similar in all five cohorts. MMP-8 is a good biological candidate for OA, but our study did not find common variants with significant association in the gene.
  • EFSA Panel Dietetic Prod Nutr; Heinonen, Marina (2017)
    Following an application from Suomen Terveysravinto Oy, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Finland, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to curcumin and normal functioning of joints. The food that is proposed as the subject of the health claim is curcumin. The Panel considers that curcumin is sufficiently characterised. The claimed effect proposed by the applicant is 'normal functioning of joints by reducing the biomarkers of inflammation'. The target population proposed by the applicant is the general population. Upon a request from EFSA to clarify whether the claimed effect is related to the normal function of joints or rather to the reduction of inflammation, the applicant did not address this issue in the reply. The Panel assumes that the claimed effect refers to the maintenance of joint function. The Panel considers that maintenance of joint function is a beneficial physiological effect. The Panel considers that no conclusions can be drawn from 15 human intervention studies conducted in patients with osteoarthritis or rheumatoid arthritis and from one study in obese subjects on serum cytokines for the scientific substantiation of the claim. In the absence of evidence for an effect of curcumin on the normal function of joints in humans, the results of the human studies on curcumin pharmacokinetics, safety and mechanistic studies, the animal studies and the in vitro studies submitted by the applicant cannot be used as a source of data for the scientific substantiation of the claim. The Panel concludes that a cause and effect relationship has not been established between the consumption of curcumin and maintenance of joint function. (C) 2017 European Food Safety Authority.
  • Mustonen, Anne-Mari; Käkelä, Reijo; Lehenkari, Petri; Huhtakangas, Johanna; Turunen, Sanna; Joukainen, Antti; Kaariainen, Tommi; Paakkonen, Tommi; Kroger, Heikki; Nieminen, Petteri (2019)
    Background: Infrapatellar fat pad (IFP) has recently emerged as a potential source of inflammation in knee arthropathies. It has been proposed to be one source of adipocytokines, fatty acids (FA), and FA-derived lipid mediators that could contribute to the pathophysiological processes in the knee joint. Alterations in synovial fluid (SF) lipid composition have been linked to both osteoarthritis (OA) and rheumatoid arthritis (RA). The aim of the present study was to compare the FA signatures in the IFP and SF of RA and OA patients. Methods: Pairs of IFP and SF samples were collected from the same knees of RA (n=10) and OA patients (n=10) undergoing total joint replacement surgery. Control SF samples (n=6) were harvested during diagnostic or therapeutic arthroscopic knee surgery unrelated to RA or OA. The FA composition in the total lipids of IFP and SF was determined by gas chromatography with flame ionization and mass spectrometric detection. Results: Arthropathies resulted in a significant reduction in the SF proportions of n-6 polyunsaturated FA (PUFA), more pronouncedly in OA than in RA. OA was also characterized with reduced percentages of 22:6n-3 and lower product/precursor ratios of n-3 PUFA. The proportions of total monounsaturated FA increased in both RA and OA SF. Regarding IFP, RA patients had lower proportions of 20:4n-6, total n-6 PUFA, and 22:6n-3, as well as lower product/precursor ratios of n-3 PUFA compared to OA patients. The average chain length of SF FA decreased in both diagnoses and the double bond index in OA. Conclusions: The observed complex alterations in the FA signatures could have both contributed to but also limited the inflammatory processes and cartilage destruction in the RA and OA knees.
  • Karjalainen, M.; Saltevo, J.; Tiihonen, M.; Haanpää, M.; Kautiainen, H.; Mäntyselkä, P. (2018)
    Background: The association between pain and diabetes in older people has been largely unexplored. The aim of this survey was to analyze the prevalence and characteristics of pain among Finnish men and women 65 or older with and without diabetes in primary care. Methods: All home-dwelling persons 65 years or older with diabetes (N = 527) and age and gender matched controls (N = 890) were identified from electronic patient records. Frequent pain was regarded as any pain experienced more often than once a week, and it was divided into pain experienced several times a week but not daily and pain experienced daily or continuously. The Numeric Rating Scale (0-10) (NRS) was used to assess the intensity and interference of the pain. Results: The number of subjects who returned the questionnaire was 1084 (76.5%). The prevalence of frequent pain in the preceding week was 50% among women without diabetes and 63% among women with diabetes (adjusted, p = 0.22). In men, the corresponding proportions were 42% without diabetes and 47% with diabetes (adjusted, p = 0.58). In both genders, depressive symptoms and the number of comorbidities were associated with pain experienced more often than once a week and with daily pain. Diabetes was not associated with pain intensity or pain interference in either women or men. Conclusions: Pain in older adults is associated with depressive symptoms and the number of comorbidities more than with diabetes itself.
  • Hamalainen, Satu; Solovieva, Svetlana; Vehmas, Tapio; Luoma, Katariina; Leino-Arjas, Paivi; Hirvonen, Ari (2014)
  • Lemmelä, Susanna; Solovieva, Svetlana; Shiri, Rahman; Benner, Christian; Heliovaara, Markku; Kettunen, Johannes; Anttila, Verneri; Ripatti, Samuli; Perola, Markus; Seppala, Ilkka; Juonala, Markus; Kahonen, Mika; Salomaa, Veikko; Viikari, Jorma; Raitakari, Olli T.; Lehtimaki, Terho; Palotie, Aarno; Viikari-Juntura, Eira; Husgafvel-Pursiainen, Kirsti (2016)
    Sciatica or the sciatic syndrome is a common and often disabling low back disorder in the working-age population. It has a relatively high heritability but poorly understood molecular mechanisms. The Finnish population is a genetic isolate where small founder population and bottleneck events have led to enrichment of certain rare and low frequency variants. We performed here the first genome-wide association (GWAS) and meta-analysis of sciatica. The meta-analysis was conducted across two GWAS covering 291 Finnish sciatica cases and 3671 controls genotyped and imputed at 7.7 million autosomal variants. The most promising loci (p
  • Barreto, Goncalo; Manninen, Mikko; Eklund, Kari K. (2020)
    Osteoarthritis (OA) has long been viewed as a degenerative disease of cartilage, but accumulating evidence indicates that inflammation has a critical role in its pathogenesis. In particular, chondrocyte-mediated inflammatory responses triggered by the activation of innate immune receptors by alarmins (also known as danger signals) are thought to be involved. Thus, toll-like receptors (TLRs) and their signaling pathways are of particular interest. Recent reports suggest that among the TLR-induced innate immune responses, apoptosis is one of the critical events. Apoptosis is of particular importance, given that chondrocyte death is a dominant feature in OA. This review focuses on the role of TLR signaling in chondrocytes and the role of TLR activation in chondrocyte apoptosis. The functional relevance of TLR and TLR-triggered apoptosis in OA are discussed as well as their relevance as candidates for novel disease-modifying OA drugs (DMOADs).
  • Svard, Tuomas; Lakovaara, Martti; Pakarinen, Harri; Haapea, Marianne; Kiviranta, Ilkka; Lammentausta, Eveliina; Jurvelin, Jukka; Tervonen, Osmo; Ojala, Risto; Nieminen, Miika (2018)
    Objective. To investigate the association of cartilage defect severity, as determined by the International Cartilage Repair Society (ICRS) grading with indentation stiffness and T2 relaxation time of magnetic resonance imaging (MRI), a biomarker for the integrity of articular cartilage. Design. Twenty-one patients scheduled for arthroscopic were included in the study. Prior to arthroscopy, subjects underwent quantitative MRI of articular cartilage, namely T2 relaxation time mapping at 1.5 T. Within 2 months, subjects underwent arthroscopy, which also included ICRS grading and measurement of arthroscopic indentation stiffness. Arthroscopic evaluations and T2 mapping at anterior, central, and posterior medial and lateral femoral condyles were correlated using a colocalization scheme. Differences in Young's modulus, as derived by indentation tests, and T2 times between ICRS grades were analyzed using Mann-Whitney's U or Kruskal-Wallis H tests. The correlation between modulus and T2 times was analyzed using Spearman's rank correlation coefficients. Results. Modulus and T2 showed significant topographical variation. In the anterior region of interest (ROI) on the medial condyle the modulus showed a negative association with ICRS grade (P = 0.040) and the T2 times were longer in ICRS grade 2 compared with grades 0 and 1 (P = 0.047). Similar, but nonsignificant associations were found in the central ROI on the medial condyle. No significant correlations were observed between the indentation modulus and T2 times. Conclusions. Cartilage degeneration is identified both with mechanical indentation and T2 mapping in MRI. However, in this study, indentation stiffness and T2 relaxation time in vivo, were not associated.
  • Finnish Shoulder Impingement (2018)
    OBJECTIVE To assess the efficacy of arthroscopic subacromial decompression (ASD) by comparing it with diagnostic arthroscopy, a placebo surgical intervention, and with a non-operative alternative, exercise therapy, in a more pragmatic setting. DESIGN Multicentre, three group, randomised, double blind, sham controlled trial. SETTING Orthopaedic departments at three public hospitals in Finland. PARTICIPANTS 210 patients with symptoms consistent with shoulder impingement syndrome, enrolled from 1 February 2005 with two year follow-up completed by 25 June 2015. INTERVENTIONS ASD, diagnostic arthroscopy (placebo control), and exercise therapy. MAIN OUTCOME MEASURES Shoulder pain at rest and on arm activity (visual analogue scale (VAS) from 0 to 100, with 0 denoting no pain), at 24 months. The threshold for minimal clinically important difference was set at 15. RESULTS In the primary intention to treat analysis (ASD versus diagnostic arthroscopy), no clinically relevant between group differences were seen in the two primary outcomes at 24 months (mean change for ASD 36.0 at rest and 55.4 on activity; for diagnostic arthroscopy 31.4 at rest and 47.5 on activity). The observed mean difference between groups (ASD minus diagnostic arthroscopy) in pain VAS were -4.6 (95% confidence interval -11.3 to 2.1) points (P=0.18) at rest and -9.0 (-18.1 to 0.2) points (P=0.054) on arm activity. No between group differences were seen between the ASD and diagnostic arthroscopy groups in the secondary outcomes or adverse events. In the secondary comparison (ASD versus exercise therapy), statistically significant differences were found in favour of ASD in the two primary outcomes at 24 months in both VAS at rest (-7.5, -14.0 to -1.0, points; P=0.023) and VAS on arm activity (-12.0, -20.9 to -3.2, points; P=0.008), but the mean differences between groups did not exceed the pre-specified minimal clinically important difference. Of note, this ASD versus exercise therapy comparison is not only confounded by lack of blinding but also likely to be biased in favour of ASD owing to the selective removal of patients with likely poor outcome from the ASD group, without comparable exclusions from the exercise therapy group. CONCLUSIONS In this controlled trial involving patients with a shoulder impingement syndrome, arthroscopic subacromial decompression provided no benefit over diagnostic arthroscopy at 24 months.
  • Skarp, Sini; Kämäräinen, Olli-Pekka; Wei, Gong-Hong; Jakkula, Eveliina; Kiviranta, Ilkka; Kröger, Heikki; Auvinen, Juha; Lehenkari, Petri; Ala-Kokko, Leena; Männikkö, Minna (2018)
    Introduction Osteoarthritis (OA) is the most common degenerative joint disease and one of the major causes of disability worldwide. It is a multifactorial disorder with a significant genetic component. The heritability of OA has been estimated to be 60% for hip OA and 39% for knee OA. Genetic factors behind OA are still largely unknown. Studying families with strong history of OA, facilitates examining the co-segregation of genetic variation and OA. The aim of this study was to identify new, rare genetic factors and novel candidate genes for OA. Methods Eight patients from three Finnish families with hip and knee OA were studied using whole exome sequencing. We focused on rare exonic variants with predicted pathogenicity and variants located in active promoter or strong enhancer regions. Expression of identified candidate genes were studied in bone and cartilage tissues and the observed variants were investigated using bioinformatic analyses. Results Two rare variants co-segregated with OA in two families. In Family 8 a missense variant (c.628C>G, p.Arg210Gly) was observed in the OLIG3 gene that encodes a transcription factor known to be associated with rheumatoid arthritis and inflammatory polyarthritis. The Arg210Gly variant was estimated to be pathogenic by Polyphen-2 and Mutation taster and the locus is conserved among mammals. In Family 12 the observed variant (c.-127G>T) was located in the transcription start site of the FIP1L1 gene. FIP1L1 participates in the regulation of polyadenylation. The c.-127G>T is located in the transcription start site and may alter the DNA-binding of transcription factors. Both, OLIG3 and FIP1L1 were observed in human bone and cartilage. Conclusion The identified variants revealed novel candidate genes for OA. OLIG3 and FIP1L1 have specific roles in transcription and may effect expression of other genes. Identified variants in these genes may thus have a role in the regulatory events leading to OA.