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Functional polymorphisms in asporin and CILP together with joint loading predispose to hand osteoarthritis.

ABSTRACT: Osteoarthritis (OA) is the most common degenerative joint disease afflicting people in the Western world and has a strong genetic influence. The aim of this study was to examine the association of two known functional polymorphisms in the TGF-? inhibiting genes, asporin (ASPN) and cartilage intermediate layer protein (CILP), with hand OA and potential gene-occupational hand loading interaction.Statistically significant interaction of the CILP rs2073711 T and ASPN D15 alleles with hand OA was observed (OR?=?2.48, 95% CI 1.27-4.85, p?=?0.008) in a Finnish hand OA cohort of 543 women (aged 45-63). When stratified by variation in working tasks, low variation of working tasks increased the risk further (OR?=?3.00, 95% CI 1.35-6.66, p?=?0.007). Based on the analysis of ASPN and CILP protein-coding regions, functional studies were performed with one observed variant, rs41278695 in the ASPN gene. Analyses showed that bone morphogenetic protein 2 (BMP2) mediated expression of aggrecan (Agc1) and type II collagen (Col2a1) was significantly suppressed (p?=?0.011 and p?=?0.023, respectively) in a murine chondrocytic cell line (ATDC5) with cells stably expressing ASPN rs41278695.The carriage of either ASPN D15 or CILP rs2073711 TT is associated with increased risk of symmetrical hand OA, particularly in individuals with low variation in work tasks. ASPN rs41278695 SNP had an effect on Agc1 and Col2a1 gene expression when induced with BMP-2 suggesting an effect on the cartilage extracellular matrix composition.

SUBMITTER: Taipale M

PROVIDER: S-EPMC5727665 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Functional polymorphisms in asporin and CILP together with joint loading predispose to hand osteoarthritis.

Taipale Mari M Solovieva Svetlana S Leino-Arjas Päivi P Männikkö Minna M

BMC genetics 20171212 1

<h4>Background</h4>Osteoarthritis (OA) is the most common degenerative joint disease afflicting people in the Western world and has a strong genetic influence. The aim of this study was to examine the association of two known functional polymorphisms in the TGF-β inhibiting genes, asporin (ASPN) and cartilage intermediate layer protein (CILP), with hand OA and potential gene-occupational hand loading interaction.<h4>Results</h4>Statistically significant interaction of the CILP rs2073711 T and AS ...[more]

PMID: 29233086

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Project description:ObjectivesThe current study quantified the influence of cartilage defect location on the tibiofemoral load distribution during gait. Furthermore, changes in local mechanical stiffness representative for matrix damage or bone ingrowth were investigated. This may provide insights in the mechanical factors contributing to cartilage degeneration in the presence of an articular cartilage defect.MethodsThe load distribution following cartilage defects was calculated using a musculoskeletal model that included tibiofemoral and patellofemoral joints with 6 degrees-of-freedom. Circular cartilage defects of 100 mm2 were created at different locations in the tibiofemoral contact geometry. By assigning different mechanical properties to these defect locations, softening and hardening of the tissue were evaluated.ResultsResults indicate that cartilage defects located at the load-bearing area only affect the load distribution of the involved compartment. Cartilage defects in the central part of the tibia plateau and anterior-central part of the medial femoral condyle present the largest influence on load distribution. Softening at the defect location results in overloading, i.e., increased contact pressure and compressive strains, of the surrounding tissue. In contrast, inside the defect, the contact pressure decreases and the compressive strain increases. Hardening at the defect location presents the opposite results in load distribution compared to softening. Sensitivity analysis reveals that the surrounding contact pressure, contact force and compressive strain alter significantly when the elastic modulus is below 7 MPa or above 18 MPa.ConclusionAlterations in local mechanical behavior within the high load bearing area resulted in aberrant loading conditions, thereby potentially affecting the homeostatic balance not only at the defect but also at the tissue surrounding and opposing the defect. Especially, cartilage softening predisposes the tissue to loads that may contribute to accelerated risk of cartilage degeneration and the initiation or progression towards osteoarthritis of the whole compartment.

Project description:Anterior cruciate ligament (ACL) injury predisposes individuals to early-onset knee joint osteoarthritis (OA). Abnormal joint loading is apparent after ACL injury and reconstruction. The relationship between altered joint biomechanics and the development of knee OA is unknown.Altered knee joint kinetics and medial compartment contact forces initially after injury and reconstruction are associated with radiographic knee OA 5 years after reconstruction.Case-control study; Level of evidence, 3.Individuals with acute, unilateral ACL injury completed gait analysis before (baseline) and after (posttraining) preoperative rehabilitation and at 6 months, 1 year, and 2 years after reconstruction. Surface electromyographic and knee biomechanical data served as inputs to an electromyographically driven musculoskeletal model to estimate knee joint contact forces. Patients completed radiographic testing 5 years after reconstruction. Differences in knee joint kinetics and contact forces were compared between patients with and those without radiographic knee OA.Patients with OA walked with greater frontal plane interlimb differences than those without OA (nonOA) at baseline (peak knee adduction moment difference: 0.00 ± 0.08 N·m/kg·m [nonOA] vs -0.15 ± 0.09 N·m/kg·m [OA], P = .014; peak knee adduction moment impulse difference: -0.001 ± 0.032 N·m·s/kg·m [nonOA] vs -0.048 ± 0.031 N·m·s/kg·m [OA], P = .042). The involved limb knee adduction moment impulse of the group with osteoarthritis was also lower than that of the group without osteoarthritis at baseline (0.087 ± 0.023 N·m·s/kg·m [nonOA] vs 0.049 ± 0.018 N·m·s/kg·m [OA], P = .023). Significant group differences were absent at posttraining but reemerged 6 months after reconstruction (peak knee adduction moment difference: 0.02 ± 0.04 N·m/kg·m [nonOA] vs -0.06 ± 0.11 N·m/kg·m [OA], P = .043). In addition, the OA group walked with lower peak medial compartment contact forces of the involved limb than did the group without OA at 6 months (2.89 ± 0.52 body weight [nonOA] vs 2.10 ± 0.69 body weight [OA], P = .036).Patients who had radiographic knee OA 5 years after ACL reconstruction walked with lower knee adduction moments and medial compartment joint contact forces than did those patients without OA early after injury and reconstruction.

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Functional polymorphisms in asporin and CILP together with joint loading predispose to hand osteoarthritis.

Publications

Functional polymorphisms in asporin and CILP together with joint loading predispose to hand osteoarthritis.

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