Association of CXCL12 Levels in Synovial Fluid with the Radiographic Severity of Knee Osteoarthritis

Xu, Qin; Sun, Xuecheng; Shang, Xiaopeng; Jiang, Housen

doi:10.2310/jim.0b013e31825f9f69

Cited by 48 publications

(42 citation statements)

References 25 publications

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“…41 Kanbe et al observed 4-fold higher levels of CXCL12 in synovial fluid, and Xu et al correlated synovial fluid levels with radiographic severity in knee osteoarthritis and suggested CXCL12 as an alternative biomarker for OA progress. 42,43 Apart from human OA cartilage CXCL2 induction was also shown in chondrocytes exposed to IL-1β, a highly upregulated cytokine during OA, 44 and Scaife et al demonstrated that CXCL12 is selectively overexpressed in OA fibroblasts rather than in rheumatoid fibroblasts. 45 The expression of genes related to cartilage (COL2A1, ACAN) and bone (COL10A1) was decreased, and genes related to ECM degradation (MMP2, MMP13, ADAM10) and inflammation (CCL2, IL8) were found induced correlating with results obtained from microarray analysis.…”

Section: ■ Discussionmentioning

confidence: 99%

Suitability of Porcine Chondrocyte Micromass Culture To Model Osteoarthritis in Vitro

et al. 2014

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In vitro tissue models are useful tools for the development of novel therapy strategies in cartilage repair and care. The limited availability of human primary tissue and high costs of animal models hamper preclinical tests of innovative substances and techniques. In this study we tested the potential of porcine chondrocyte micromass cultures to mimic human articular cartilage and essential aspects of osteoarthritis (OA) in vitro. Primary chondrocytes were enzymatically isolated from porcine femoral condyles and were maintained in 96-multiwell format to establish micromass cultures in a high-throughput scale. Recombinant porcine tumor necrosis factor alpha (TNF-α) was used to induce OA-like changes documented on histological (Safranin O, collagen type II staining), biochemical (hydroxyproline assay, dimethylmethylene blue method), and gene expression level (Affymetrix porcine microarray, real time PCR) and were compared with published data from human articular cartilage and human micromass cultures. After 14 days in micromass culture, porcine primary chondrocytes produced ECM rich in proteoglycans and collagens. On gene expression level, significant correlations of detected genes with porcine cartilage (r = 0.90), human cartilage (r = 0.71), and human micromass culture (r = 0.75) were observed including 34 cartilage markers such as COL2A1, COMP, and aggrecan. TNF-α stimulation led to significant proteoglycan (-75%) and collagen depletion (-50%). Comparative expression pattern analysis revealed the involvement of catabolic enzymes (MMP1, -2, -13, ADAM10), chemokines (IL8, CCL2, CXCL2, CXCL12, CCXL14), and genes associated with cell death (TNFSF10, PMAIPI, AHR) and skeletal development (GPNMB, FRZB) including transcription factors (WIF1, DLX5, TWIST1) and growth factors (IGFBP1, -3, TGFB1) consistent with published data from human OA cartilage. Expression of genes related to cartilage ECM formation (COL2A1, COL9A1, COMP, aggrecan) as well as hypertrophic bone formation (COL1A1, COL10A1) was predominantly found decreased. These findings indicating significant parallels between human articular cartilage and the presented porcine micromass model and vice versa confirm the applicability of known cartilage marker and their characteristics in the porcine micromass model. TNF-α treatment enabled the initiation of typical OA reaction patterns in terms of extensive ECM loss, cell death, formation of an inflammatory environment through the induction of genes coding for chemokines and enzymes, and the modulation of genes involved in skeletal development such as growth factors, transcription factors, and cartilage ECM-forming genes. In conclusion, the porcine micromass model represents an alternative tissue platform for the evaluation of innovative substances and techniques for the treatment of OA.

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Section: ■ Discussionmentioning

confidence: 99%

Suitability of Porcine Chondrocyte Micromass Culture To Model Osteoarthritis in Vitro

et al. 2014

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“…An SDF-1 blockade effect has been detected in guinea pigs with primary osteoarthritis; in these guinea pigs, catabolic breakdown products released from chondrocytes decreased, compared with untreated controls. 11 Stromal cell-derived factor-1 has been measured in synovial fluid and serum in humans and guinea pigs with osteoarthritis, 7,8,[11][12][13] but to our knowledge, has not been evaluated in horses. A guinea pig study revealed large increases in synovial fluid concentrations in animals with primary osteoarthritis and PTOA.…”

Section: Coefficient Of Variation Mmpmentioning

confidence: 99%

Concentrations of stromal cell-derived factor-1 in serum, plasma, and synovial fluid of horses with osteochondral injury

Dymock¹,

Brown²,

Merritt³

et al. 2014

ajvr

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Results suggested that serum SDF-1 concentrations were more sensitive than plasma and synovial fluid concentrations for detection of osteochondral injury in the fetlock or carpal joint of racehorses. Analysis of serum and synovial SDF-1 concentrations in horses with experimentally induced joint injury may help define the onset and progression of post-traumatic osteoarthritis and aid in the evaluation of anti-inflammatory treatments.

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“…As shown in Table 2 and Fig. 3 (heatmap for common regulated gene), several genes have been previously shown to associate with both RA and OA, such as CXCL12 (Asquith et al, 2015;Xu et al, 2012), MMP-1 (Abd-Allah et al, 2012), TGFB3 (Kapetanakis et al, 2010;Kruger et al, 2010) and PPARG (Palma et al, 2012;Vasheghani et al, 2015). Among these common DEGs, the upregulated genes MDK (Weckbach et al, 2012) and HLA-DMB (Morel et al, 2004) and the down-regulated genes FABP4 (Andres Cerezo et al, 2013) and BCL6 (Baecklund et al, 2006) have been previously reported to be associated with RA, whereas there is no definite conclusion about the roles of genes TNFRSF11A, RGS19, ADCY1, TRIM14, TK1, APOBEC3G, ITPKC, AMPH, DDIT4, MIR1908, APOD, SFPQ and CITED1 in RA pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Identifying genes related with rheumatoid arthritis via system biology analysis

Liu

Lin

2015

Gene

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Association of CXCL12 Levels in Synovial Fluid with the Radiographic Severity of Knee Osteoarthritis

Abstract: CXCL12 levels in SF were closely related to the radiographic severity of OA. CXCL12 levels in SF may be an alternative biomarker for the progression of OA.

Cited by 48 publications

References 25 publications

Suitability of Porcine Chondrocyte Micromass Culture To Model Osteoarthritis in Vitro

Suitability of Porcine Chondrocyte Micromass Culture To Model Osteoarthritis in Vitro

Concentrations of stromal cell-derived factor-1 in serum, plasma, and synovial fluid of horses with osteochondral injury

Identifying genes related with rheumatoid arthritis via system biology analysis

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