Biochemical Characterization of Early Osteoarthritis in the Ankle

Schmal, Hagen; Salzmann, Gian M.; Langenmair, Elia; Henkelmann, Ralf; Südkamp, Norbert P.; Niemeyer, Philipp

doi:10.1155/2014/434802

Cited by 21 publications

(24 citation statements)

References 40 publications

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“…Aggrecan has been identified as a reliable indicator for OA progression and matrix degradation [ 22 ] that is upregulated following injury or general inflammation. Both the breakdown of extracellular matrix (ECM) and enhanced synovial secretion are known to cause this effect [ 23 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical Trial and In Vitro Study for the Role of Cartilage and Synovia in Acute Articular Infection

Langenmair

Kubosch

Salzmann

et al. 2015

Mediators of Inflammation

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Objective. Osteoarthritis is a long-term complication of acute articular infections. However, the roles of cartilage and synovia in this process are not yet fully understood. Methods. Patients with acute joint infections were enrolled in a prospective clinical trial and the cytokine composition of effusions compared in patients with arthroplasty (n = 8) or with intact joints (n = 67). Cytokines and cell function were also analyzed using a human in vitro model of joint infection. Results. Synovial IL-1β levels were significantly higher in patients with arthroplasty (p = 0.004). Higher IL-1β concentrations were also found in the in vitro model without chondrocytes (p < 0.05). The anti-inflammatory cytokines IL-4 and IL-10 were consistently expressed in vivo and in vitro, showing no association with the presence of cartilage or chondrocytes. In contrast, FasL levels increased steadily in vitro, reaching higher levels without chondrocytes (p < 0.05). Likewise, the viability of synovial fibroblasts (SFB) during infection was higher in the presence of chondrocytes. The cartilage-metabolism markers aggrecan and bFGF were at higher concentrations in intact joints, but also synthesized by SFB. Conclusions. Our data suggest an anti-inflammatory effect of cartilage associated with the SFBs' increased resistance to infections, which displayed the ability to effectively synthesize cartilage metabolites.The trial is registered with DRKS 00003536, MISSinG.

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Section: Discussionmentioning

confidence: 99%

Clinical Trial and In Vitro Study for the Role of Cartilage and Synovia in Acute Articular Infection

Langenmair

Kubosch

Salzmann

et al. 2015

Mediators of Inflammation

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“…Byproducts from cartilage and synovium metabolism accumulate in synovial fluid (SF). SF thereby serves as a repository for quantifiable markers indicating ankle health . Therefore, analysis of ankle joint SF for potential biomarkers could be clinically relevant for early detection of PTOA, especially before signs of OA are visible by radiograph .…”

Section: Introductionmentioning

confidence: 99%

Attenuated levels of ghrelin in synovial fluid is related to the disease severity of ankle post‐traumatic osteoarthritis

Zou

Yang³

et al. 2019

BioFactors

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Post‐traumatic osteoarthritis (PTOA) of ankle joints results in pain and reduced joint function. Ghrelin, a 28‐amino‐acid polypeptide, has been previously identified as the first cognate natural ligand that binds to the growth hormone secretagogue receptor. In the present study, ghrelin has been validated to exert cartilage‐protective and anti‐inflammatory effects. The current study was aimed at investigating the potential role of the levels of serum and synovial fluid (SF) ghrelin on the severity of disease in patients suffering from ankle PTOA. Ninety‐seven patients with ankle osteoarthritis who received an arthroscopical examination and debridement or replacement of the ankle joint were included in the study cohort. Meanwhile, 95 healthy individuals (whose age and sex were matched) who received periodic body checkups were enrolled as healthy controls. Enzyme‐linked immunosorbent assay (ELISA) was used to analyze the ghrelin levels in serum and SF. SF was also probed for cartilage degradation enzyme matrix metalloproteinases‐3 (MMP‐3) and tumor necrosis factor alpha (TNF‐α), which is a known pro‐inflammatory cytokine. The clinical evaluation was carried out using the American Orthopedic Foot and Ankle Society (AOFAS) ankle‐hindfoot rating scale and visual analogue scale (VAS). The radiographic severity was evaluated using the modified Kellgren–Lawrence (K–L) grading system. We scored for the modified Mankin's score to depict histopathological changes due to cartilage lesions. The diagnostic relevance of the ghrelin concentrations in the prediction of the radiographic grading (in comparison with MMP‐3 and TNF‐α) was evaluated by calculating the area under the curve of the receiver operating characteristic (ROC) curve. The serum abundance of ghrelin was not significantly altered between ankle PTOA patients and healthy controls. SF ghrelin was negatively correlated with radiographic progression determined by modified ankle K–L grades. In addition SF ghrelin concentrations were negatively related to VAS scores, and positively associated with AOFAS ankle‐hindfoot rating. Moreover, SF ghrelin was inversely proportional to the expressions of MMP‐3 and TNF‐α. ROC analysis curve demonstrated that ghrelin serves as a favorable marker for the diagnosis of radiographic severity by modified ankle K‐L grade. The ghrelin concentration in SF is negatively proportional to disease progression in patients suffering from ankle PTOA. Local administration of ghrelin may function as a decent adjuvant therapy to delay the progress of ankle PTOA. © 2019 BioFactors, 45(3):463–470, 2019

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“…This composite structure endows cartilage extracellular matrix (ECM) with compressive strength and articular cartilage with shock-absorbing properties (Mead and Apte, 2018). Loss of aggrecan is a milestone in early stage OA, because aggrecan prevents loss of collagen fibrils (Scanzello et al, 2011;Verma and Dalal, 2011;Schmal et al, 2014;Apte, 2016). Therefore, guaranteeing the integrity of aggrecan is important for ameliorating OA.…”

Section: Discussionmentioning

confidence: 99%

AMD3100 Attenuates Post-Traumatic Osteoarthritis by Maintaining Transforming Growth Factor-β1-Induced Expression of Tissue Inhibitor of Metalloproteinase-3 via the Phosphatidylinositol 3-Kinase/Akt Pathway

Shi

et al. 2020

Front. Pharmacol.

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AMD3100 is a small-molecule inhibitor of the C-X-C motif chemokine ligand 12/C-X-C chemokine receptor type 4 (CXCL12/CXCR4) axis, while its role in aggrecan metabolism is unclear. We hypothesized that the AMD3100 modulates the transforming growth factor-b1 (TGF-b1)-induced expression of tissue inhibitor of metalloproteinase-3 (TIMP-3) in chondrocytes. We evaluated expression of CXCL12/CXCR4 and TIMP-3 in the knee joints of rats with and without osteoarthritis (OA) by immunohistochemistry, immunofluorescence, Western blotting, and enzyme-linked immunosorbent assay (ELISA). The rats were divided into sham control, destabilization of the medial meniscus/ AMD3100-treated (DMM/AMD3100-treated), and DMM/phosphate-buffered saline (PBS)treated groups. After 6 weeks, the rats were euthanized and subjected to histological and immunohistochemical analyses. Also, interleukin (IL)-1-pretreated primary chondrocytes were cultured in the presence of empty control (−, −), CXCL12a (+,−), CXCL12a + small interfering RNA (siRNA) CXCR4 (+,+), or CXCL12a + siNC (+NC), and the expression levels of target markers were evaluated by Western blotting and real-time reverse transcription PCR (RT-PCR). The CXCL12/CXCR4 levels were higher, and the expression of TIMP-3 was lower, in the OA rats compared to the healthy control rats. The rats in the DMM/AMD3100treated group revealed a markedly decreased immunological response and mild pathology. Treatment with CXCL12a increased expression of aggrecan and disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5) and suppressed that of TIMP-3 in IL-1-pretreated primary chondrocytes. TGF-b1 increased expression of TIMP-3, and this increase was reversed by CXCL12a via the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Moreover, these effects were inhibited by the CXCR4 antagonist

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Biochemical Characterization of Early Osteoarthritis in the Ankle

Cited by 21 publications

References 40 publications

Clinical Trial and In Vitro Study for the Role of Cartilage and Synovia in Acute Articular Infection

Clinical Trial and In Vitro Study for the Role of Cartilage and Synovia in Acute Articular Infection

Attenuated levels of ghrelin in synovial fluid is related to the disease severity of ankle post‐traumatic osteoarthritis

AMD3100 Attenuates Post-Traumatic Osteoarthritis by Maintaining Transforming Growth Factor-β1-Induced Expression of Tissue Inhibitor of Metalloproteinase-3 via the Phosphatidylinositol 3-Kinase/Akt Pathway

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