Methods. One hundred and seven knee OA patients and 50 age- and sex-matched healthy participants attended a 1-h QST session. Testing was performed on the medial side of the knee and the pain-free forearm. Light-touch thresholds were assessed using von Frey filaments, pressure pain thresholds using a digital pressure algometer, and thermal sensation and pain thresholds using a Thermotest MSA. Significant differences in median threshold values from knee OA patients and healthy participants were identified using Mann–Whitney U-tests. The z-score transformations were used to determine the prevalence of the different somatosensory abnormalities in knee OA patients.

Results. Testing identified 70% of knee OA patients as having at least one somatosensory abnormality. Comparison of median threshold values between knee OA patients and healthy participants revealed that patients had localized thermal and tactile hypoaesthesia and pressure hyperalgesia at the osteoarthritic knee. Tactile hypoaesthesia and pressure hyperalgesia were also present at the pain-free forearm. The most prevalent somatosensory abnormalities were tactile hypoaesthesia and pressure hyperalgesia, evident in between 20 and 34% of patients.

Conclusion. This study found that OA patients demonstrate an array of somatosensory abnormalities, of which the most prevalent were tactile hypoaesthesia and pressure hyperalgesia. Further research is now needed to establish the clinical implications of these somatosensory abnormalities.

Methods. In this observational cohort study, levels of different dimensions of fatigue were measured in knee and/or hip OA patients before and after 12 weeks of conservative treatment. Cross-sectional and longitudinal relations between (change in) fatigue dimensions and (change in) pain or physical function were studied using association models, controlling for predefined possible confounders.

Results. A total of 231 patients was included, with 47% experiencing severe fatigue. A small decrease in levels of fatigue was seen after standardized treatment. The level of fatigue severity was cross-sectionally and longitudinally associated with physical function, whereas the level of physical fatigue was cross-sectionally and longitudinally associated with pain and physical function. No confounders were identified.

Conclusions. Important levels of fatigue are common in knee and hip OA patients. After evidence-based tailored conservative treatment targeted to improve pain and physical function, a small decrease in fatigue levels was found. Reduction in levels of different fatigue dimensions were related to the change in physical function and pain.

Methods. A total of 313 undiagnosed subjects, who first visited Keio University Hospital with joint symptoms, including arthralgia, joint swelling and morning stiffness, without any previous treatment except for NSAIDs, were included in the present study. A clinical diagnosis of RA was made by rheumatologists, and the gold standard diagnosis of RA was defined as an indication for instituting DMARDs for RA.

Results. Seventy-six subjects were diagnosed as gold standard RA. Among these, 8 did not have any swollen joints, 50 were classified as definite RA under the 2010 criteria and the other 18 as not having RA. Eighty-two subjects were eligible for the 2010 criteria, and the sensitivity and specificity under the 2010 criteria were 73.5 and 71.4%, respectively, compared with 47.1 and 92.9% under the 1987 criteria. But the sensitivity of the 2010 criteria decreased to 15.8% when both RF and anti-CCP were negative. According to the result of a receiver-operated characteristic (ROC) curve of the scoring system, if swollen joints and differential diagnosis are not accurately detected, it would be better to use a score of 5 as the cut-off level to detect RA.

Conclusion. The 2010 classification criteria have a high sensitivity and have been verified to be useful for distinguishing RA at an early stage.

Methods. STR/ORT mice were housed individually and fed diets with or without Asp-Phe-OMe (4 mg/kg), after weaning at the age of 3 weeks, until 15 months of age (average of 20 animals per group). The study groups were kept blinded to the investigators, who measured food consumption and body weight and performed gait mobility tests. Radiographic scans were also performed at regular time intervals to evaluate differential radiographic anomalies associated with progress of OA in response to oral Asp-Phe-OMe therapy.

Results. The Asp-Phe-OMe-fed animals presented a pattern of significantly delayed disease onset. In addition, their muscle and bone mass were highly preserved, even at later time points after OA was established. Moreover, control animals presented a higher variability in gait motility in comparison with the Asp-Phe-OMe-fed animals, suggesting a protective effect from movement limitations associated with advanced OA.

Conclusion. Asp-Phe-OMe, given orally, delays OA in the spontaneous STR/ORT model, improves bone cortical density and muscle mass, and may contribute to a better quality of life for these diseased animals.

In the present study, titanium surfaces were functionalized by four different self-assembled monolayers (SAMs) forming methoxy silanes: (1) hexadecyltrimethoxysilane, (2) dimethoxymethyloctylsilane, (3) allyltrimethylsilane, and (4) 3-aminopropyltrimethoxysilane. In addition, calf skin type-I collagen was cross-linked to the SAM surface 3-aminopropyltrimethoxysilane by means of two different treatments: (1) N-hydroxysuccinimide and (2) glutaraldehyde. The functionalized titanium surfaces were coated with recombinant human β-defensin-2 (rHuβD2), an antimicrobial peptide, and were tested for antibacterial activity against Escherichia coli. The release of rHuβD2 was quantified by means of enzyme-linked immunosorbent assay (ELISA).

The coating of functionalized titanium surfaces with rHuβD2 was successful. Recombinant HuβD2 was eluted from the titanium surfaces continuously, yielding antimicrobial activity up to several hours. Antimicrobial activity with a killing rate of 100% was observed for all functionalized titanium surfaces after two hours of incubation. The dimethoxymethyloctylsilane-functionalized titanium surface delivered 0.65 µg of rHuβD2 after six hours with a 60% bacterial killing rate. The silane-functionalized surfaces exhibited a faster release of antimicrobially active rHuβD2 compared with collagen modifications.

Natural antibiotics such as rHuβD2 integrated into the metal surface of titanium implants may be a promising tool to prevent and control infections around orthopaedic implants.

This kind of titanium surface modification may provide an alternative treatment of serious, life-threatening infections related to prosthetic implant surgery.

Sixty New Zealand White rabbits received either complete or partial (medial half) transection of the anterior cruciate ligament or sham surgery (control) on the left knee. At the time that the animals were killed at eight or sixteen weeks postoperatively (ten animals for each treatment and/or test-period combination), the experimental knees were subjected to sagittal plane stability measurement, followed by whole-joint cartilage histological evaluation with use of the Mankin score.

Sagittal plane instability created in the partial transection group was intermediate between those in the complete transection and sham surgery groups. The partial and complete transection groups exhibited cartilage degeneration on the medial femoral and/or medial tibial surfaces. The average histological score (and standard deviation) for the medial compartment in the partial transection group (2.9 ± 0.9) was again intermediate, significantly higher than for the sham surgery group (1.9 ± 0.8) and significantly lower than for the complete transection group (4.5 ± 2.3). The average histological scores for the medial compartment in the partial transection group correlated significantly with the magnitude of instability, with no threshold effect being evident. The significance level of alpha was set at 0.05 for all tests.

The severity of cartilage degeneration increased continuously with the degree of instability in this survival rabbit knee model of graded instability.

These results are supportive of the current intuitively based concept for orthopaedic treatment of unstable joints, which is that surgical reconstruction to reduce pathological joint instability contributes to prevention of posttraumatic osteoarthritis regardless of the degree of instability initially present.

Six hundred and sixty elderly Koreans (sixty-five years or older) were evaluated for radiographic severity of knee osteoarthritis on the basis of the Kellgren-Lawrence grading system and also for symptom severity on the basis of the Western Ontario and McMaster Universities Osteoarthritis Index scales. Patient interviews and a questionnaire that made use of a geriatric depression scale were conducted for the purpose of assessing depressive disorders. Regression analyses were performed to assess the relative contributions by radiographic severity and depression severity to Western Ontario and McMaster Universities Osteoarthritis Index scores and to explore any associations between radiographic severity and the presence of a depressive disorder with regard to the risk of symptomatic knee osteoarthritis. Symptomatic knee osteoarthritis was defined as a Western Ontario and McMaster Universities Osteoarthritis Index score of ≥39.

The presence of a depressive disorder was found to be associated with an increased risk of symptomatic knee osteoarthritis (odds ratio = 5.87 [95% confidence interval, 3.01 to 11.44]). However, the influence of the presence of a depressive disorder was limited to subjects with a radiographic severity of minimal to moderate (Kellgren-Lawrence grade 0 to 3). The presence of a depressive disorder was not associated with the risk of symptomatic knee osteoarthritis in subjects with severe osteoarthritis (Kellgren-Lawrence grade 4).

This study indicates that the assessment and management of coexisting depression should be integrated with the assessment and management of knee osteoarthritis, particularly when radiographic changes of osteoarthritis in the knee joint are not severe.

Methods. A total of 153 subjects aged 25–60 years, 81% female, were recruited. MRI was performed of the dominant knee. Cartilage volume was measured using validated methods. Total body BMD and content was measured using DXA.

Results. Total body BMC and BMD was significantly associated with medial cartilage volume in both sexes. However, the associations were stronger in men for BMC (B = 0.52; 95% CI 0.21, 0.83; P for difference = 0.001) and BMD (B = 2242; 95% CI 443, 4041; P for difference = 0.05). Similar results were obtained in the lateral tibial compartment. No significant association was obtained between total body BMD and BMC and patella cartilage volume in either men or women.

Conclusions. In this relatively healthy population, we found a positive relationship between total body BMD and BMC and tibial cartilage volume in the medial and lateral compartments. These relationships were stronger in men than women. Thus, the results of this study may provide some insight into the sex differences in knee cartilage volume, which may in turn facilitate our understanding of the pathogenesis of OA.

The present prospective study included thirty patients with knee pain, mechanical symptoms, and magnetic resonance imaging findings that were positive for a meniscal tear who chose arthroscopic partial meniscectomy after unsuccessful nonoperative management. Synovial fluid was aspirated at the time of surgery and was assayed for the fibronectin-aggrecan complex with use of a heterogeneous enzyme-linked immunosorbent assay (ELISA). The results were compared with knee aspirates from ten asymptomatic volunteers with no pain who underwent magnetic resonance imaging of the knee.

The mean optical density (and standard deviation) of the fibronectin-aggrecan complex was significantly greater in synovial fluid from knees undergoing arthroscopic surgery as compared with fluid from asymptomatic controls (13.29 ± 8.48 compared with 0.03 ± 0.09; p < 0.001). The mean age in the study group was significantly greater than in control group (46.0 ± 12.6 compared with 38.5 ± 6.0 years; p = 0.02), but controlling for age did not affect the results. Post hoc, an optical density cutoff value of 0.3 distinguished the study group from the control group with 100% accuracy.

A novel fibronectin-aggrecan complex is present in the synovial fluid of painful knees with meniscal abnormality. The fibronectin-aggrecan complex may prove to be useful as a clinical biomarker or therapeutic target. Further research is warranted to correlate functional outcome after surgery with the fibronectin-aggrecan complex and other cartilage biomarkers.

Diagnostic Level IV. See Instructions to Authors for a complete description of levels of evidence.

This investigation was a single-blinded, prospective, randomized, controlled noninferiority trial. Sixty-five participants were randomized to receive a six-week program of outpatient physical therapy either in the conventional manner or by means of an Internet-based telerehabilitation program. The primary outcome measure was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) measured at baseline and six weeks by a blinded independent assessor. Secondary outcomes included the Patient-Specific Functional Scale, the timed up-and-go test, pain intensity, knee flexion and extension, quadriceps muscle strength, limb girth measurements, and an assessment of gait. Noninferiority was assessed through the comparison of group differences with a noninferiority margin and with linear mixed model statistics.

Baseline characteristics between groups were similar, and all participants had significant improvement on all outcome measures with the intervention (p < 0.01 for all). After the six-week intervention, participants in the telerehabilitation group achieved outcomes comparable to those of the conventional rehabilitation group with regard to flexion and extension range of motion, muscle strength, limb girth, pain, timed up-and-go test, quality of life, and clinical gait and WOMAC scores. Better outcomes for the Patient-Specific Functional Scale and the stiffness subscale of the WOMAC were found in the telerehabilitation group (p < 0.05). The telerehabilitation intervention was well received by participants, who reported a high level of satisfaction with this novel technology.

The outcomes achieved via telerehabilitation at six weeks following total knee arthroplasty were comparable with those after conventional rehabilitation.

Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence.

Methods. One hundred and nine men and women with symptomatic knee OA were recruited. The same knee was imaged using MRI at baseline and ~2 years later. Tibial cartilage volume and BMLs were measured. Knee joint replacement over 4 years was determined.

Results. The mean age of the subjects at baseline was 63.2 (s.d. 10.3) years. BMLs were present in 66% of the subjects. Cross-sectionally, BMLs were negatively associated with both medial (regression coefficient –121.4; 95% CI –183.8, –859.1; P < 0.001) and lateral (regression coefficient –142.1; 95% CI –241.8, –42.4; P = 0.01) tibial cartilage volume data. Longitudinally, for every 1-score increase in baseline BML severity (range 0–4), the annual total tibial cartilage loss was increased by 1.14% (95% CI 0.29%, 1.87%; P = 0.01). The risk of knee joint replacement over 4 years increased with increasing BML score (odds ratio 1.57; 95% CI 1.04, 2.35; P = 0.03).

Conclusion. The prevalence and severity of BMLs are associated with less tibial cartilage volume and greater cartilage loss over 2 years. Moreover, severity of BMLs was positively associated with risk of knee joint replacement over 4 years. This provides further support for the importance of BMLs in identifying those with OA most likely to progress. Identifying factors that prevent or reduce the severity of BMLs may provide an important target in the prevention of disease progression and treatment of OA, and the subsequent need for arthroplasty.

Methods. A total of 153 subjects aged 25–60 years, 81% females, were recruited across a range of BMI (18–55 kg/m2) for a study examining the relationship between obesity and musculoskeletal disease. MRI was performed of the dominant knee. Cartilage volume, defects and BMLs were measured using validated methods. Body composition was measured using dual X-ray absorptiometry.

Results. There was an 81 (95% CI: 69, 94) mm3 increase in cartilage volume for every 1 kg increase in skeletal muscle mass. Fat mass was not significantly associated with cartilage volume. Fat mass, but not skeletal muscle mass, was a risk factor for cartilage defects and BMLs. For every 1 kg increase in total body fat there was an increased risk of cartilage defects (OR = 1.31, 95% CI: 1.04, 1.64) and BMLs (OR = 1.09, 95% CI: 1.01, 1.18).

Conclusions. In this relatively healthy population, fat mass was associated with increased cartilage defects and BMLs, which are features of early knee OA. In contrast, skeletal muscle mass was positively associated with cartilage volume, which may be due to coinheritance, a commonality of environmental factors associated with cartilage accrual or a protective effect of increased muscle.

Methods. Survey data from 13 986 people aged ≥50 years who took part in the North Staffordshire Osteoarthritis Project were linked to a database of primary care consultations. Foot problems were defined as responding affirmatively to the questions: ‘Have you had any problems with your feet over the last year?’ or ‘Have you had pain in the last year in and around the foot?’. The main outcome measure was a record of a musculoskeletal foot-related consultation within 18 months following the survey.

Results. Of the 3858 participants with foot problems who had not consulted before the survey, 350 (9.1%) consulted in the 18 months following the survey. Age, sex, education, general health and pain in other regions were not associated with future consultation. However, those who consulted were more likely to have reported foot pain [adjusted odds ratio (OR) 2.04; 95% CI 1.22, 3.42) and to consider treatments to be effective in controlling disease (OR 1.54; 95% CI 1.07, 2.21) in the baseline survey, and to have been a frequent consulter in the 18 months before the survey (OR 1.65; 95% CI 1.30, 2.09).

Conclusions. Only a minority of older people with musculoskeletal foot problems consult their general practitioner about them. Foot pain, frequent consultation for other problems and positive perceptions of treatment efficacy appear to be the strongest factors influencing future consultation.

Methods. Locked nucleotide analogue (LNA)-modified miR-34a-specific anti-sense was transfected into rat chondrocyte monolayer culture. After that, IL-1β was added to the chondrocytes to create an OA model in vitro. The effect of silencing miR-34a on the prevention of chondrocyte apoptosis was analysed by assessment of the expression levels of Col2a1 and iNOS, also through assessment of cell viability and TUNEL staining.

Results. The expression of miR-34a was significantly up-regulated by IL-1β. Silencing of miR-34a significantly prevented IL-1β-induced down-regulation of Col2a1, as well as IL-1β-induced up-regulation of iNOS. Finally, MiR-34a inhibitor could also reduce TUNEL-positive cells.

Conclusion. Silencing of miR-34a by LNA-modified anti-sense could effectively reduce rat chondrocyte apoptosis induced by IL-1β. This present study revealed that silencing of miR-34a might develop a novel intervention for OA treatment through the prevention of cartilage degradation.

Methods. Osteochondral junctions from medial tibial plateaux of patients undergoing arthroplasty for RA (n = 10) or OA (n = 11), or from non-arthritic post-mortem controls (n = 11) were characterized by immunohistochemistry for CD34 and smooth muscle -actin (blood vessels), CD68 (macrophages), CD3 (lymphocytes), proliferating cell nuclear antigen, vascular endothelial, platelet-derived and nerve growth factor (NGF).

Results. Osteochondral angiogenesis was demonstrated as increased endothelial cell proliferation and vascular density in non-calcified articular cartilage, both in RA and OA. Osteochondral angiogenesis was associated with subchondral bone marrow replacement by fibrovascular tissue expressing VEGF, and with increased NGF expression within vascular channels. RA was characterized by greater lymphocyte infiltration and PDGF expression than OA, whereas chondrocyte expression of VEGF was a particular feature of OA. NGF was observed in vascular channels that contained calcitonin gene-related peptide-immunoreactive sensory nerve fibres.

Conclusions. Osteochondral angiogenesis in RA and OA is associated with growth factor expression by cells within subchondral spaces, vascular channels and by chondrocytes. NGF expression and sensory nerve growth may link osteochondral angiogenesis to pain in arthritis.

The study, published in the Annals of the New York Academy of Sciences, compared H2S in blood samples and knee joint synovial fluid from rheumatoid arthritis patients, osteoarthritis patients, and healthy people. Rheumatoid arthritis patients had higher concentrations of H2S in their synovial fluid compared to controls. Higher levels were linked to disease activity amd lowered counts of inflammatory cells. This suggests H2S may play a role in controlling inflammation -- and this opens the door to further research and potential development of H2S-based treatments.

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Knee Arthritis - Hydrogen Sulfide Is Present in Joint Fluid originally appeared on About.com Arthritis on Sunday, August 22nd, 2010 at 23:14:25.

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Methods. AQPs were detected in synovial tissue samples from patients with OA and RA using RT–PCR and immunohistochemistry. Fibroblast-like synoviocytes (FLSs) from patients with OA and RA were cultured and stimulated with TNF-. The expression of AQPs in FLSs was examined using RT–PCR and western blot analyses and the function of aquaglyceroporins was examined by a glycerol uptake assay.

Results. AQP1, -3 and -9 mRNAs were expressed in synovial tissues from patients with OA and RA. AQP1, -3 and -9 proteins were also detected by immunohistochemistry. AQP9 mRNA was expressed more strongly in the synovial tissues of OA patients with hydrarthrosis than those without. AQP9 mRNA and protein expression were strongly induced with TNF- treatment in FLSs, whereas the expression of AQP1 and -3 mRNAs was not induced with TNF- treatment. AQP9 as an aquaglyceroporin was induced by TNF-.

Conclusions. AQP9 mRNA was detected in synovial tissues from OA and RA patients with hydrarthrosis. AQP9 expression was strongly induced in FLSs with TNF-. Although the functions of AQP1, -3 and -9 in synovial tissues remain to be elucidated, it suggested that AQP9 might be related to the pathogenesis of hydrarthrosis and inflammatory synovitis.

Microfracture and other bone marrow stimulation techniques involve penetration of the subchondral plate in order to recruit mesenchymal stem cells into the chondral defect. The formation of a stable clot that fills the lesion is of paramount importance to achieve a successful outcome.

Mosaicplasty is a viable option with which to address osteochondral lesions of the knee and offers the advantage of transplanting hyaline cartilage. However, limited graft availability and donor site morbidity are concerns.

Transplantation of an osteochondral allograft consisting of intact, viable articular cartilage and its underlying subchondral bone offers the ability to address large osteochondral defects of the knee, including those involving an entire compartment.

The primary theoretical advantage of autologous chondrocyte implantation is the development of hyaline-like cartilage rather than fibrocartilage in the defect, which presumably leads to better long-term outcomes and longevity of the healing tissue.

Use of synthetic scaffolds is a potentially attractive alternative to traditional cartilage procedures as they are readily available and, unlike allogeneic tissue transplants, are associated with no risk of disease transmission. Their efficacy, however, has not been proven clinically.

Methods. FLS from patients with either RA or OA were co-cultured with peripheral blood mononuclear cells (PBMCs), and incubated with various drugs for 6 days. Subsequently, apoptosis induction was detected by Nucleosome ELISA and terminal deoxynucleotidyl transferase dUTP nick end labeling. Western blot was used to determine the activation of the phosphatase and tensin homologue deleted on chromosome 10 (PTEN)-focal adhesion kinase (FAK) pathway as well as Bax and Bcl-2 levels. Immunoprecipitation was used for studying phosphorylation of transmembrane TNF- (tmTNF-).

Results. All the tested drugs induced apoptosis of FLSs in the presence of PBMCs obtained from the same patient only when the two cell populations were in direct contact by activating the PTEN–FAK pathway and increasing Bax levels. This effect was not due to antibody-dependent cell-mediated cytotoxicity. Only the two antibodies infliximab and adalimumab were able to up-regulate Bcl-2.

Conclusions. Etanercept is more effective in inducing FLS apoptosis compared with the other drugs tested. This induction is dependent on the presence of PBMCs, and involves the activation of PTEN–FAK pathway. Bcl-2 increase induced by the monoclonal antibodies infliximab and adalimumab may play a protective role and thus counteract their pro-apoptotic effect on FLSs.

Methods. Fatigue was assessed using the Multidimensional Assessment of Fatigue-Global Fatigue Index (MAF-GFI) in 103 patients with RA and 103 with OA. Sleep disturbance and pain were assessed using a visual analogue scale anxiety and depression using the Hospital Anxiety and Depression scale and disability using the HAQ. In the RA cohort, the disease activity score-28 joint count (DAS-28) and the Van der Heijde modified Sharp score were calculated, and in the OA cohort, the Kellgren–Lawrence score and the WOMAC score calculated.

Results. The MAF-GFI scores were higher in the OA cohort (P = 0.02). This was not significant after controlling for disability (P = 0.59). OA participants reported greater pain, disability, depression and sleeplessness than those with RA (all P < 0.01). The strongest correlates of fatigue in the RA cohort were depression (P < 0.001) and anxiety (P < 0.001). There was no significant association with pain (P = 0.43), DAS-28 (P = 0.07), HAQ (P = 0.10) or Sharp score (P = 0.78). In OA, the correlates of fatigue were older age (P = 0.02), sleep disturbance (P = 0.03), depression (P = 0.04), disability (P = 0.04) and lower CRP (P = 0.001).

Conclusions. Fatigue is common and severe in both RA and OA. In RA, fatigue had no significant association with pain, disease activity, disability or erosions, but was associated with depression and anxiety. The disparity in correlates indicates that generalizing the experience of fatigue between OA and RA is not appropriate. Fatigue is an important domain in the assessment of disease impact.

Methods. We searched MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials for all reports published since 1966 of RCTs, evaluating either the efficacy of joint lavage alone or of joint lavage combined with steroid injection for knee OA on pain intensity and physical function. The time point for evaluation was a priori fixed at 3 months. Effect size (ES) was calculated to compare results across studies.

Results. From the 49 articles identified, reports of six RCTs were analysed for a total of 855 OA patients (511 in the treatment group and 344 in the control group). The pooled ES of the joint lavage vs placebo was not significant for pain intensity [ES = 0.17 (–0.37, 0.71)] or physical function [ES = –0.15 (–0.34, 0.04)], nor was the pooled ES of joint lavage combined with steroid injection vs joint lavage alone significant for pain intensity [ES = –0.82 (–2.47, 0.82)] or physical function [ES = 0.09 (–0.28, 0.45)].

Conclusions. This meta-analysis of RCTs investigating joint lavage for knee OA suggests that at 3 months, (i) joint lavage alone does not provide significant improvement in pain or function and (ii) the combination of joint lavage and IA steroid injection is no more efficacious than lavage alone.

Methods. Focused on major health problems, the survey was carried out in 1978–80 in a sample of 8000 subjects, representative of the Finnish population aged >=30 years. Altogether 823 subjects free from knee OA at the baseline were re-examined in 2000–01, and after the intervening 22 years 94 new cases of knee OA were found. Knee OA was diagnosed on both occasions by physicians using information on disease histories, symptoms and standardized clinical examinations.

Results. The risk of developing knee OA was strongly associated with BMI (kg/m2); adjusted for age and gender and other covariates, and compared with the reference category (BMI < 25.0); the relative odds ratios (ORs) with 95% CIs were 1.7 (95% CI 1.0, 2.8) and 7.0 (95% CI 3.5, 14.10) for subjects with BMIs 25.0–29.9 and >=30.0, respectively. Similarly, the adjusted OR for the heaviest category of physical stress at work was 18.3 (95% CI 4.2, 79.4) compared with the lightest category, and 5.1 (95% CI 1.4, 19.0) for permanent complaints due to past knee injury.

Conclusions. This prospective study confirms the roles of obesity, heavy work load and knee injury in the aetiology of knee OA.

Methods. Micromass pellets of human articular chondrocytes were cocultured for up to 28 days with human periosteal explants either with physical contact or separated by a membrane allowing paracrine interactions only. Quantitative reverse transcription (RT)–PCR, ELISA, immunohistochemistry and collagen isolation were used to analyse the expression and secretion of TGF-β1, collagens I and II and chondrogenic differentiation markers such as MIA (CD-RAP) and aggrecan.

Results. TGF-β1 gene expression was induced significantly in paracrine cocultures in periosteum, whereas it was repressed in physical contact cocultures. However, a higher TGF-β1 secretion rate was observed in physical contact cocultures compared with periosteal monocultures. The expression of COL2A1, melanoma inhibitory activity (cartilage-derived retinoic acid-sensitive protein) [MIA (CD-RAP)] and aggrecan was mainly unaffected by culture conditions, whereas COL1A1 gene expression was increased in periosteal paracrine cocultures. Collagen I staining was induced in micromass pellets from paracrine cocultures, whereas it was repressed in chondrocytes from physical contact cocultures.

Conclusions. We found evidence for a bidirectional regulating system with paracrine signalling pathways between periosteum and articular chondrocytes. Stimulation of TGF-β1 and COL1A1 gene expression in periosteal paracrine cocultures and the increased release of TGF-β1 protein in physical contact conditions indicate an anabolic, and not merely chondrogenic micro-environment in this in vitro model for periosteal-based ACI.

DNA samples from 129 patients with Kashin-Beck disease (the Kashin-Beck disease group), seventy-two healthy control subjects from areas where Kashin-Beck disease was endemic (control group 1), and forty-eight healthy control subjects from areas where Kashin-Beck disease was not endemic (control group 2) were collected, and fifteen short tandem repeats were genotyped. The allele frequencies of these short tandem-repeat loci were compared among the three groups. Differences in selenium concentrations among patients and controls were also examined, and the interaction between low selenium levels and the susceptibility loci was calculated.

The percentages of subjects with short tandem-repeat alleles D2S338 (290 bp) and D11S4094 (194 bp) in the Kashin-Beck disease group were significantly lower than those in the two control groups, while percentages of D2S305 (320 bp) and D11S4149 (221 bp) were higher than those in the control groups. The percentage of subjects with D11S4149 (217 bp) in the Kashin-Beck disease group was only significantly lower than that in control group 1. The percentages of subjects with D11S912 (106 bp) in both the Kashin-Beck disease group and control group 1 were significantly lower than those in control group 2. Selenium concentrations in serum from subjects in the Kashin-Beck disease group and control group 1 were similar, but both were lower than that of control group 2. The odds ratios of low selenium in serum were between 1.2 and 1.6 (p > 0.05), and the odds ratios of interactions between low selenium and the susceptibility loci ranged between 0.8 and 1.4 (p > 0.05).

Our results suggest that variants of the chromosomal short tandem repeats D11S4094, D11S4149, D2S338, and D2S305 are associated with Kashin-Beck disease, and that the frequency of D11S912 polymorphisms varies in geographic areas with high and low prevalences of Kashin-Beck disease. Our data did not show a significant interaction between low selenium and the susceptibility loci in the occurrence of Kashin-Beck disease. The interaction between genetic variabilities and environmental factors can be complex, but our results suggest that genetic factors may be more important than selenium deficiency in the pathogenesis of Kashin-Beck disease.