Functional analysis of synovial fluid from osteoarthritic knee and carpometacarpal joints unravels different molecular profiles.

OBJECTIVE: In this work, we aimed to elucidate the molecular mechanisms driving primary OA. By studying the dynamics of protein expression in two different types of OA joints we searched for similarities and disparities to identify key molecular mechanisms driving OA. METHODS: For this purpose, human SF samples were obtained from CMC-I OA and knee joint of OA patients. SF samples were analysed by label-free quantitative liquid chromatography mass spectrometry. Disease-relevant proteins identified in proteomics studies, such as clusterin, paraoxonase/arylesterase 1 (PON1) and transthyretin were validated by enzyme-linked immunosorbent assays, and on the mRNA level by droplet digital PCR. Functional studies were performed in vitro using primary chondrocytes. RESULTS: Differential proteomic changes were observed in the concentration of 40 proteins including clusterin, PON1 and transthyretin. Immunoassay analyses of clusterin, PON1, transthyretin and other inflammatory cytokines confirmed significant differences in protein concentration in SF of CMC-I and knee OA patients, with primarily lower protein expression levels in CMC-I. Functional studies on chondrocytes unequivocally demonstrated that stimulation with SF obtained from knee OA, in contrast to CMC-I OA joint, caused a significant upregulation in pro-inflammatory response, cell death and hypertrophy. CONCLUSION: This study demonstrates that differential expression of molecular players in SF from different OA joints evokes diverse effects on primary chondrocytes. The pathomolecular mechanisms of OA may significantly differ in various joints, a finding that brings a new dimension into the pathogenesis of primary OA.

Associations between biomarkers of joint metabolism, hand osteoarthritis, and hand pain and function: the Johnston County Osteoarthritis Project.

OBJECTIVE: To determine the associations between joint metabolism biomarkers and hand radiographic osteoarthritis [(rOA), based on Kellgren Lawrence (KL) grade ≥ 2], symptoms, and function. METHODS: Cross-sectional data were available for 663 participants (mean age 63 yrs, 63% white, 49% women). Three definitions of hand rOA were considered: (1) a composite measure involving at least 3 hand joints distributed bilaterally with 2 of 3 in the same joint group, including ≥ 1 distal interphalangeal joint, without metacarpophalangeal (MCP) swelling; (2) rOA in at least 1 joint of a group; and (3) number of joints with KL ≥ 2. We assessed hand symptoms and the 15-item Australian Canadian Hand Osteoarthritis Index (AUSCAN; Likert format). We measured serum cartilage oligomeric matrix protein (sCOMP), hyaluronic acid (sHA), carboxy-terminal propeptide of type II collagen, type II collagen degradation product, urinary C-terminal crosslinked telopeptide of type II collagen, and urinary N-terminal crosslinked telopeptide. Linear regression models were performed to assess associations between each biomarker with hand rOA, AUSCAN, and symptoms, adjusting for age, sex, race, current smoking/drinking status, body mass index, and hip and knee rOA. RESULTS: In adjusted analyses, MCP (p < 0.0001) and carpometacarpal rOA (p = 0.003), and a higher number of hand joints with rOA (p = 0.009), were associated with higher levels of sHA. Positive associations were seen between AUSCAN and hand symptoms and levels of sCOMP (p ≤ 0.003) and sHA (p ≤ 0.048). CONCLUSION: Hand symptoms and higher AUSCAN scores were independently associated with higher levels of both sCOMP and sHA; hand rOA was associated only with sHA levels.

Relationship of relaxin hormone and thumb carpometacarpal joint arthritis.

BACKGROUND: The female predominance in thumb carpometacarpal (CMC) joint arthritis has led to speculation that reproductive hormones or hypermobility are responsible. Evidence shows that patients with pathologic laxity have a higher rate of thumb CMC arthritis. Relaxin hormone increases laxity in the pelvic ligaments through upregulation of matrix metalloproteases (MMPs). It is thus a hormone of interest in the development of thumb CMC arthritis. QUESTIONS/PURPOSES: Our goals were to identify demographic and hormonal factors associated with joint laxity in patients with CMC arthritis and to evaluate the relationship among serum relaxin, relaxin receptors, and MMPs in the anterior oblique ligament (AOL) of the thumb. We hypothesized that serum relaxin was correlated with joint laxity as well as with relaxin receptors and MMPs in the AOL. METHODS: Forty-nine patients undergoing thumb CMC arthroplasty underwent laxity examination, blood draw, and AOL sampling. Ligaments were analyzed for relaxin receptor and MMPs 1 and 3 using quantitative reverse-transcriptase polymerase chain reaction. RESULTS: Women demonstrated more joint laxity than men (p < 0.001). RNA analysis confirmed relaxin receptors in the AOL as well as MMPs 1 and 3. There was a significant correlation between serum relaxin and MMP-1 (p = 0.04). Detectable serum relaxin was negatively correlated with relaxin receptors in the AOL (p = 0.02). CONCLUSIONS: Further studies are needed to evaluate the role of laxity and sex hormones in thumb CMC arthritis. CLINICAL RELEVANCE: Relaxin hormone may play a role in the development of arthritis at the thumb CMC joint. LEVEL OF EVIDENCE: Level I, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Inverse dynamic analysis of the biomechanics of the thumb while pipetting: a case study.

Thumb-push manual pipettes are commonly used tools in many medical, biological, and chemical laboratories. Epidemiological studies indicate that the use of thumb-push mechanical pipettes is associated with musculoskeletal disorders in the hand. The goal of the current study was to evaluate the kinematics and joint loading of the thumb during pipetting. The time-histories of joint angles and the interface contact force between the thumb and plunger during the pipetting action were determined experimentally, and the joint loadings and joint power in the thumb were calculated via an inverse dynamic approach. The moment, power, and energy absorption in each joint of the thumb during the extraction and dispensing actions were analyzed. The results indicate that the majority of the power is generated in the interphalangeal (IP) and carpometacarpal (CMC) joints for the pipetting action. The analysis method and results in the current study will be helpful in exploring the mechanism for musculoskeletal injuries of the hand associated with pipetting, providing a preliminary foundation for ergonomic design of the pipette.

Do metabolic factors add to the effect of overweight on hand osteoarthritis? The Rotterdam Study.

BACKGROUND: As hand joints are non-weight bearing, the association between overweight and hand osteoarthritis (HOA) is critical to understanding how overweight may associate with osteoarthritis (OA) apart from axial load. Overweight might be associated with the occurrence of OA through other metabolic factors. AIM: To evaluate the role of overweight in HOA, cross-sectional data of a population-based study were used (> or =55 years, n = 3585). The role of diabetes, hypertension and total cholesterol:high-density lipoprotein (HDL)-cholesterol ratio on HOA, and whether they play an intermediate role in the association of overweight/HOA was investigated. Furthermore, the prevalence of HOA in the concurrent presence of overweight and other metabolic factors was evaluated. RESULTS: Independently of other metabolic factors, overweight (body mass index (BMI) >27.4 kg/m(2)) showed a significant association with HOA (OR 1.4, 95% CI 1.2 to 1.7). The association between diabetes and HOA was only present in people aged 55-62 years (OR 1.9, 95% CI 1.0 to 3.8), but was absent in the total population or in other age groups. The association of hypertension with HOA was weak, and disappeared after adjustment for BMI. The total/HDL cholesterol ratio showed no significant association with HOA. The concurrent presence of overweight, diabetes and hypertension resulted in an even higher prevalence of HOA (OR 2.3, 95% CI 1.3 to 3.9) compared with subjects with none of these characteristics; this prevalence increased further in the younger age group (OR 3.2, 95% CI 1.1 to 8.8). CONCLUSION: No intermediate effect of metabolic factors on the association of overweight with HOA was found. An increase in the prevalence of HOA, however, seems to be present when overweight occurs together with hypertension and diabetes especially at a relatively young age.