Osteoarthritis year in review 2015: mechanics

Objective The two main objectives of the study include 1) Test the hypothesis that the lateral femoral condyle (LFC) in patients with primary OA and varus knees undergoing total knee arthroplasty (TKA) can be used as a model to better characterize varying histological features of human OA. 2) Correlate characteristic OA features using the established histopathological scoring systems (HHGS and OARSI) to understand potential histopathological patterns of OA initiation. Design Two osteochondral specimens (4×4×8mm) were collected from fifty patient’s LFC at the time of TKA (total 100 specimens), who presented preserved lateral knee compartment with joint space width >2mm. Three independent readers graded the sections on three different occasions using HHGS and OARSI systems. The correlation between individual parameters of the two scoring systems and their inter- and intra-reader variability, reliability and reproducibility were estimated. Results All samples in this cohort showed abnormal histopathological features. Total histopathological scores of the LFC ranged from HHGS median=4.6 (range=0 to 11), and OARSI median=5.2 (range=0 to 19.5). The four individual sub-items of HHGS scoring system (structure, cells, safraninO staining, tidemark) were weakly correlated, with the correlation between structure and cellularity being the strongest (r=0.40). Both the scoring systems had similar repeatability and reproducibility coefficients of <21%. Conclusions OA changes in the LFC are not confined to any one region, and maybe seen in different regions of cartilage, tidemark, subchondral bone, and/or the marrow space vascularity. These variations may point to the possibility of several potential patterns of initiation in OA.

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“…It is associated with changes in local and systemic inflammatory mediators, genetic factors and innate immunity. [2–7]…”

Section: Introductionmentioning

confidence: 99%

Histopathological assessment of primary osteoarthritic knees in large patient cohort reveal the possibility of several potential patterns of osteoarthritis initiation

Mantripragada

Piuzzi

Zachos

et al. 2017

Current Research in Translational Medicine

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“…It is not only the magnitude of the load but also the location of the load that influences damage, as more damage is observed on the medial surface of the tibia [9]. Knee adduction in the gait has been associated with femoral cartilage changes, and external knee flexion has been associated with more tibial cartilage changes [10]. Obesity has been associated with increased mechanical loading on the joint, as well as altering one’s gait.…”

Section: Pathophysiology Of Osteoarthritismentioning

confidence: 99%

Damage-associated molecular patterns in the pathogenesis of osteoarthritis: potentially novel therapeutic targets

et al. 2017

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Osteoarthritis (OA) is a chronic disease that degrades the joints and is often associated with increasing age and obesity. The two most common sites of OA in adults are the knee and hip joints. Increased mechanical stress on the joint from obesity can cause the articular cartilage to degrade and release damage associated molecular patterns (DAMPs). These DAMPs are involved in various molecular pathways that interact with nuclear factor-kappa B (NF-κB) and result in the transcription of inflammatory cytokines and activation of matrix metalloproteinases (MMP) that progressively destroy cartilage. This review focuses on the interactions and contribution to the pathogenesis and progression of OA through the DAMPs: high mobility group box 1 (HMGB-1), the receptor for advanced glycation end-products (RAGE), the alarmin proteins S100A8 and S100A9, and heparan sulfate. HMGB-1 is released from damaged or necrotic cells and interacts with toll-like receptors (TLRs) and RAGE to induce inflammatory signals, as well as behave as an inflammatory cytokine to activate innate immune cells. RAGE interacts with HMGB-1, advanced glycation end-products, and innate immune cells to increase local inflammation. The alarmin proteins are released following cell damage and interact through TLRs to increase local inflammation and cartilage degradation. Heparan sulfate has been shown to facilitate the binding of HMGB-1 to RAGE and could play a role in the progression of OA. Targeting these DAMPs may be potential therapeutic strategies for the treatment of OA.

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“…Both normal physiologic and pathologic overload forces are known to regulate cellular responses in essentially all musculoskeletal connective tissues [2]. Many previous studies revealed that alter joint loading patterns could lead to OA progression [3,4].…”

Section: Introductionmentioning

confidence: 99%

Elevated Expression of Periostin in Cartilage in Early Experimental Osteoarthritis

Zhang¹

2017

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Osteoarthritis (OA) is characterized by the degeneration of affected joints leading to pain and reduced mobility.Periostin appears as a potential candidate in transducing mechanical signals to stimulate chondrocyte proliferation. 15 rats (E-group) underwent both medial meniscectomy and medial collateral ligament (MCL) transaction, while the other 15 rats (S-group) underwent sham surgery. Animals were killed at 1, 2, and 4 weeks postsurgery, and 5 animals were put into use per-time point in each treatment group. Cartilage was harvested from tibial plateau and femoral condyle. We examined the level of Postn expression in cartilage of the experimental OA, using real-time PCR and immunohistochemistry analysis. The expression of Postn was about 2-fold higher at 1 week (P=0.08<0.05), 4-fold higher at 2 weeks (P=0.003<0.05) and 4-fold higher at 4 weeks (P=0.034<0.05) post-surgery in E-group compared to S-group. Postn protein expression levels were markedly increased in the E-Group compared with the S-Group at 1, 2 and 4 weeks post-surgery. This study will be of benefit to those subsequent studies using the OA model to evaluate the outcomes of Postn epxpression in mechanism of OA. Postn may play prominent roles in pathogenic mechanisms of OA.

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Osteoarthritis year in review 2015: mechanics

Cited by 95 publications

References 76 publications

Histopathological assessment of primary osteoarthritic knees in large patient cohort reveal the possibility of several potential patterns of osteoarthritis initiation

Histopathological assessment of primary osteoarthritic knees in large patient cohort reveal the possibility of several potential patterns of osteoarthritis initiation

Damage-associated molecular patterns in the pathogenesis of osteoarthritis: potentially novel therapeutic targets

Elevated Expression of Periostin in Cartilage in Early Experimental Osteoarthritis

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