Introduction

We aimed to describe the distribution of radiographic chondrocalcinosis (CC) and to examine whether metacarpophalangeal joint (MCPJ) calcification and CC at other joints occurs in the absence of knee involvement.

Methods

This was a cross-sectional study embedded in the Genetics of Osteoarthritis and Lifestyle study (GOAL). All participants (n = 3,170) had radiographs of the knees, hands, and pelvis. These were scored for radiographic changes of osteoarthritis (OA), for CC at knees, hips, symphysis pubis, and wrists, and for MCPJ calcification. The prevalence of MCPJ calcification and CC overall, at each joint, and in the presence or absence of knee involvement, was calculated.

Results

The knee was the commonest site of CC, followed by wrists, hips, and symphysis pubis. CC was more likely to be bilateral at knees and wrists but unilateral at hips. MCPJ calcification was usually bilateral, and less common than CC at knees, hips, wrists, and symphysis pubis. Unlike that previously reported, CC commonly occurred without any knee involvement; 44.4% of wrist CC, 45.9% of hip CC, 45.5% of symphysis pubis CC, and 31.3% of MCPJ calcification occurred in patients without knee CC. Those with meniscal or hyaline articular cartilage CC had comparable ages (P = 0.21), and neither preferentially associated with fibrocartilage CC at distant joints.

Conclusions

CC visualized on a plain radiograph commonly occurs at other joints in the absence of radiographic knee CC. Therefore, knee radiographs alone are an insufficient screening test for CC. This has significant implications for clinical practice, for epidemiologic and genetic studies of CC, and for the definition of OA patients with coexistent crystal deposition.

Osteoarthritis (OA) is the most common form of arthritis and a major cause of disability. This study evaluates the association in Caucasian populations of two single nucleotide polymorphisms (SNPs) mapping to the Human Leukocyte Antigen (HLA) region and deriving from a genome wide association scan (GWAS) of knee OA in Japanese populations. The frequencies for rs10947262 were compared in 36,408 controls and 5,749 knee OA cases from European-descent populations. rs7775228 was tested in 32,823 controls and 1,837 knee OA cases of European descent. The risk (major) allele at rs10947262 in Caucasian samples was not significantly associated with an odds ratio (OR)  = 1.07 (95%CI 0.94 -1.21; p = 0.28). For rs7775228 the meta-analysis resulted in OR = 0.94 (95%CI 0.81-1.09; p = 0.42) for the allele associated with risk in the Japanese GWAS. In Japanese individuals these two SNPs are in strong linkage disequilibrium (LD) (r2 = 0.86) with the HLA class II haplotype DRB1*1502 DQA1*0103 DQB1*0601 (frequency 8%). In Caucasian and Chinese samples, using imputed data, these SNPs appear not to be in LD with that haplotype (r2<0.07). The rs10947262 and rs7775228 variants are not associated with risk of knee OA in European descent populations and they do not appear tag the same HLA class II haplotype as they do in Japanese individuals.

Introduction

Although the presence of bone marrow lesions (BMLs) on magnetic resonance images is strongly associated with osteoarthritis progression and pain, the underlying pathology is not well established. The aim of the present study was to evaluate the architecture of subchondral bone in regions with and without BMLs from the same individual using bone histomorphometry.

Methods

Postmenopausal female subjects (n = 6, age 48 to 90 years) with predominantly medial compartment osteoarthritis and on a waiting list for total knee replacement were recruited. To identify the location of the BMLs, subjects had a magnetic resonance imaging scan performed on their study knee prior to total knee replacement using a GE 1.5 T scanner with a dedicated extremity coil. An axial map of the tibial plateau was made, delineating the precise location of the BML. After surgical removal of the tibial plateau, the BML was localized using the axial map from the magnetic resonance image and the lesion excised along with a comparably sized bone specimen adjacent to the BML and from the contralateral compartment without a BML. Cores were imaged via microcomputed tomography, and the bone volume fraction and tissue mineral density were calculated for each core. In addition, the thickness of the subchondral plate was measured, and the following quantitative metrics of trabecular structure were calculated for the subchondral trabecular bone in each core: trabecular number, thickness, and spacing, structure model index, connectivity density, and degree of anisotropy. We computed the mean and standard deviation for each parameter, and the unaffected bone from the medial tibial plateau and the bone from the lateral tibial plateau were compared with the affected BML region in the medial tibial plateau.

Results

Cores from the lesion area displayed increased bone volume fraction but reduced tissue mineral density. The samples from the subchondral trabecular lesion area exhibited increased trabecular thickness and were also markedly more plate-like than the bone in the other three locations, as evidenced by the lower value of the structural model index. Other differences in structure that were noted were increased trabecular spacing and a trend towards decreased trabecular number in the cores from the medial location as compared with the contralateral location.

Conclusions

Our preliminary data localize specific changes in bone mineralization, remodeling and defects within BMLs features that are adjacent to the subchondral plate. These BMLs appear to be sclerotic compared with unaffected regions from the same individual based on the increased bone volume fraction and increased trabecular thickness. The mineral density in these lesions, however, is reduced and may render this area to be mechanically compromised, and thus susceptible to attrition.

Structural transition in chromatin was measured as a function of counter ions in solution (NaCl or MgCl2) and of histones bound on the DNA. The addition of counter ions to aqueous solutions of chromatin, partially dehistonized chromatin, and DNA caused a drastic reduction in viscosity and a significant increase in sedimentation coefficient. Transitions occurred primarily at about 2 × 10−3 M NaCl and 1 × 10−5 M MgCl2 and are interpreted as a change in structure of chromatin induced by tight binding of cations (Na+ or Mg++) to DNA, either free or bound by histones, and is an intrinsic property of DNA rather than of the type of histone bound. At a given ionic condition, removal of histone H1 from chromatin had only a minor effect on the hydrodynamic properties of chromatin while removal of other histones caused a drastic change in these properties. An increase in the sedimentation coefficient of DNA was observed also for protamine. DNA complexes wherein the bound protein contains only unordered coil rather than the α-helices found in histones.

Objective

To assess if a coding variant in the gene encoding transient receptor potential cation channel, subfamily V, member 1 (TRPV1) is associated with genetic risk of painful knee osteoarthritis (OA).

Methods

The Ile585Val TRPV1 variant encoded by rs8065080 was genotyped in 3270 cases of symptomatic knee OA, 1098 cases of asymptomatic knee OA and 3852 controls from seven cohorts from the UK, the USA and Australia. The genetic association between the low-pain genotype Ile–Ile and risk of symptomatic and asymptomatic knee OA was assessed.

Results

The TRPV1 585 Ile–Ile genotype, reported to be associated with lower thermal pain sensitivity, was associated with a lower risk of symptomatic knee OA in a comparison of symptomatic cases with healthy controls, with an odds ratio (OR) of 0.75 (95% CI 0.64 to 0.88; p=0.00039 by meta-analysis) after adjustment for age, sex and body mass index. No difference was seen between asymptomatic OA cases and controls (OR=1.02, 95% CI 0.82 to 1.27 p=0.86) but the Ile–Ile genotype was associated with lower risk of symptomatic versus asymptomatic knee OA adjusting for covariates and radiographic severity (OR=0.73, 95% CI 0.57 to 0.94 p=0.0136). TRPV1 expression in articular cartilage was increased by inflammatory cytokines (tumour necrosis factor α and interleukin 1). However, there were no differences in TRPV1 expression in healthy and arthritic synovial tissue.

Conclusions

A genotype involved in lower peripheral pain sensitivity is significantly associated with a decreased risk of painful knee OA. This indicates a role for the pro-nociceptive gene TRPV1 in genetic susceptibility to symptomatic knee OA, which may also be influenced by a role for this molecule in cartilage function.

Objective

Knee osteoarthritis (OA) has a significant genetic component. The authors have assessed the role of three variants reported to influence risk of knee OA with p<5×10–8 in determining patellofemoral and tibiofemoral Kellgren Lawrence (K/L) grade in knee OA cases.

Methods

3474 knee OA cases with sky-line and weight-bearing antero-posterior x-rays of the knee were selected based on the presentation of K/L grade ≥2 at either the tibiofemoral or patellofemoral compartments for one or both knees. Patients belonging to three UK cohorts, were genotyped for rs143383, rs4730250 and rs11842874 mapping to the GDF5, COG5 and MCF2L genes, respectively. The association between tibiofemoral K/L grade and patellofemoral K/L grade was assessed after adjusting for age, gender and body mass index.

Results

No significant association was found between the rs4730250 and radiographic severity. The rs11842874 mapping to MCF2L was found to be nominally significantly associated with patellofemoral K/L grade as a quantitative trait (p=0.027) but not as a binary trait. The GDF5 single nucleotide polymorphism rs143383 was associated with tibiofemoral K/L grade (β=0.05 (95% CI 0.02 to 0.08) p=0.0011).

Conclusions

Our data indicate that within individuals affected by radiographic knee OA, OAGDF5 has a modest but significant effect on radiographic severity after adjustment for the major risk factors.