Serum and synovial fluid chemokine ligand 2/monocyte chemoattractant protein 1 concentrations correlates with symptomatic severity in patients with knee osteoarthritis

Li, Liang; Jiang, Baoen

doi:10.1177/0004563214545117

Cited by 70 publications

(59 citation statements)

References 27 publications

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“…At later stages, also other CCR2 ligands (CCL2, CCL8, CCL7 and CCL13) are detectable in articular cartilage. These findings are consistent with human studies that noted increased human CCL2 and CCR2 in patients with OA(35, 36). …”

Section: Discussionsupporting

confidence: 92%

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Role of the C-C chemokine receptor-2 in a murine model of injury-induced osteoarthritis

Longobardi

Temple

Tagliafierro

et al. 2017

Osteoarthritis and Cartilage

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Objective We previously found in our embryonic studies that proper regulation of the chemokine CCL12 through its sole receptor CCR2, is critical for joint and growth plate development. In the present study, we examined the role of CCR2 in injury-induced-osteoarthritis (OA). Method We used a murine model of injury-induced-OA (destabilization of medial meniscus, DMM), and systemically blocked CCR2 using a specific antagonist (RS504393) at different times during disease progression. We examined joint degeneration by assessing cartilage (cartilage loss, chondrocyte hypertrophy, MMP-13 expression) and bone lesions (bone sclerosis, osteophytes formation) with or without the CCR2 antagonist. We also performed pain behavioral studies by assessing the weight distribution between the normal and arthritic hind paws using the IITS incapacitance meter. Results Testing early vs. delayed administration of the CCR2 antagonist demonstrated differential effects on joint damage. We found that OA changes in articular cartilage and bone were ameliorated by pharmacological CCR2 blockade, if given early in OA development: specifically, pharmacological targeting of CCR2 during the first 4 weeks following injury, reduced OA cartilage and bone damage, with less effectiveness with later treatments. Importantly, our pain-related behavioral studies showed that blockade of CCR2 signaling during early, 1–4wks post-surgery or moderate, 4–8wks post-surgery, OA was sufficient to decrease pain measures, with sustained improvement at later stages, after treatment was stopped. Conclusions Our data highlight the potential efficacy of antagonizing CCR2 at early stages to slow the progression of post-injury OA and, in addition, improve pain symptoms.

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Section: Discussionsupporting

confidence: 92%

“…Consistent with studies suggesting a role as a mediator of OA pain (14,15, 36), we were also able to demonstrate that CCR2 signaling inhibition reduced pain by examining joint loading as a measure of pain response.…”

Section: Discussionsupporting

confidence: 88%

Role of the C-C chemokine receptor-2 in a murine model of injury-induced osteoarthritis

Longobardi

Temple

Tagliafierro

et al. 2017

Osteoarthritis and Cartilage

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“…Recently, it was reported that levels of CCL2, a major monocyte chemoattractant in serum and synovial fluid obtained from individuals with OA correlated positively with pain and physical disability 15. Further, microarray analyses of genes expressed in knees of mice with surgery-induced OA showed that Ccl2 is upregulated as early as 6 hours and 7 days after surgery when there is no apparent histological changes) relative to sham-operated controls (see online supplementary figure S1A).…”

Section: Resultsmentioning

confidence: 96%

“…Additional studies have reported that synovium from individuals with joint injuries such as meniscal tears, a major risk factor for OA development, have elevated chemokine expression suggesting that these chemokines might instigate inflammatory responses in such individuals 13 14. Furthermore, a recent study reported that synovial fluid levels of CCL2 (or MCP-1) correlated positively with pain and physical disability in patients with OA 15. In line with this, it has been shown that deficiency in CCR2, the main receptor for CCL2, reduces OA-related pain mouse OA 16.…”

Section: Introductionmentioning

confidence: 99%

CCL2/CCR2, but not CCL5/CCR5, mediates monocyte recruitment, inflammation and cartilage destruction in osteoarthritis

et al. 2016

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Objectives While various monocyte chemokine systems are increased in expression in osteoarthritis (OA), the hierarchy of chemokines and chemokine receptors in mediating monocyte/macrophage recruitment to the OA joint remains poorly defined. Here, we investigated the relative contributions of the CCL2/CCR2 versus CCL5/ CCR5 chemokine axes in OA pathogenesis. Methods Ccl2-, Ccr2-, Ccl5- and Ccr5-deficient and control mice were subjected to destabilisation of medial meniscus surgery to induce OA. The pharmacological utility of blocking CCL2/CCR2 signalling in mouse OA was investigated using bindarit, a CCL2 synthesis inhibitor, and RS-504393, a CCR2 antagonist. Levels of monocyte chemoattractants in synovial tissues and fluids from patients with joint injuries without OA and those with established OA were investigated using a combination of microarray analyses, multiplexed cytokine assays and immunostains. Results Mice lacking CCL2 or CCR2, but not CCL5 or CCR5, were protected against OA with a concomitant reduction in local monocyte/macrophage numbers in their joints. In synovial fluids from patients with OA, levels of CCR2 ligands (CCL2, CCL7 and CCL8) but not CCR5 ligands (CCL3, CCL4 and CCL5) were elevated. We found that CCR2+ cells are abundant in human OA synovium and that CCR2+ macrophages line, invade and are associated with the erosion of OA cartilage. Further, blockade of CCL2/CCR2 signalling markedly attenuated macrophage accumulation, synovitis and cartilage damage in mouse OA. Conclusions Our findings demonstrate that monocytes recruited via CCL2/CCR2, rather than by CCL5/CCR5, propagate inflammation and tissue damage in OA. Selective targeting of the CCL2/CCR2 system represents a promising therapeutic approach for OA.

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“…Specially, CCL3 is elevated in pre-X-ray-defined patients and CCL3 has a high ability to discriminate pre-X-ray patients from healthy people, suggesting CCL3 is a potential diagnostic marker for early detection of the disease [86]. Recently, it was reported that CCL2 concentrations in SF are positively correlated with pain score as defined by WOMAC, suggesting that CCL2 is a marker for symptomatic severity of OA [97]. …”

Section: Inflammatory Markersmentioning

confidence: 99%

Review of Prospects of Biological Fluid Biomarkers in Osteoarthritis

Nguyen

Sharma

Chakraborty

et al. 2017

IJMS

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Osteoarthritis (OA) is a degenerative disease of the joints and is one of the leading causes of disability in adults. However, there are no key therapeutics for OA and medical treatment is based on managing the symptoms and slowing down progression of the disease. Diagnostics based on clinical examination and radiography have provided little information about metabolic changes in joint tissues, disease onset and progression. Due to lack of effective methods for early detection and evaluation of treatment outcome, the measurement of biochemical markers (biomarkers) shows promise as a prospective method aiding in disease monitoring. OA biomarkers that are present in biological fluids such as blood, urine and synovial fluid, sources that are easily isolated from body, are of particular interest. Moreover, there are increasingly more studies identifying and developing new biomarkers for OA. In this review, efforts have been made to summarize the biomarkers that have been reported in recent studies on patients. We also tried to classify biomarkers according to tissue metabolism (bone, cartilage and synovial metabolism markers), pathological pathways (inflammatory and genetic markers) and biological function (chemokines, growth factors, acute phase proteins, etc.).

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Serum and synovial fluid chemokine ligand 2/monocyte chemoattractant protein 1 concentrations correlates with symptomatic severity in patients with knee osteoarthritis

Cited by 70 publications

References 27 publications

Role of the C-C chemokine receptor-2 in a murine model of injury-induced osteoarthritis

Role of the C-C chemokine receptor-2 in a murine model of injury-induced osteoarthritis

CCL2/CCR2, but not CCL5/CCR5, mediates monocyte recruitment, inflammation and cartilage destruction in osteoarthritis

Review of Prospects of Biological Fluid Biomarkers in Osteoarthritis

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