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AB0799 Decreased ratio of TIMP1/MMP-9 is associated with higher pain sensitivity in a subset of osteoarthritic patients with low mechanistic target of rapamicin gene expression in the peripheral blood
  1. EV Tchetina1,
  2. GA Markova1,
  3. EA Taskina2,
  4. NG Kashevarova2,
  5. EP Sharapova2,
  6. LI Alekseeva2
  1. 1Immunology & Molecular Biology
  2. 2Osteoarthritis, Nasonova Research Institute of Rheumatology, Moscow, Russian Federation

Abstract

Background Progression of osteoarthritis (OA) produces loss of articular cartilage that may culminate in pain, loss of joint function, and disability. Osteoarthritic changes in articular cartilage are associated with progressive proteolytic degradation of the extracellular matrix due to excessive expression of metalloproteinases (MMPs) over their tissue inhibitors (TIMPs). At the same time, decrease in TIMP concentration versus MMP has been previously associated with an increase in pain sensitivity.

Objectives Here we hypothesized that imbalance in TIMP1 and MMP-9 gene and protein expressions in the peripheral blood might contribute to pain perception in OA patients.

Methods We examined whole blood of 65 OA outpatients and 27 healthy subjects. Clinical testing comprised physical examination, radiographic and WOMAC scoring, and ultrasonography. Total RNA isolated from the whole blood was used for gene expression examination of mTOR, mechanistic target of rapamycin, a major regulator of cell growth and proliferation, metalloproteinase MMP-9, and tissue inhibitor of metalloproteinase, TIMP1 using quantitative Real-time RT-PCR. p70-S6K (mTOR read-out), MMP-9, and TIMP1 protein levels were quantified by ELISA.

Results 23 OA outpatients exhibited significant downregulation of mTOR gene expression (subset “Low mTOR”) while other 42 OA outpatients have demonstrated upregulation of mTOR gene expression (subset “High mTOR”) in the peripheral blood compared to healthy controls. Although both OA outpatient subsets had comparable radiographic severity according to Kellgren-Lawrence grading, similar age, disease duration, and body mass index, “Low mTOR” patients experienced significantly higher pain at joint function versus “High mTOR” subset. This was associated with a significant upregulation of MMP-9 gene expression in “Low mTOR” patients versus healthy subjects while TIMP1 expression remained equal to controls. In a “High mTOR” subset, both gene expressions were significantly upregulated. p70-S6K and TIMP1 protein concentrations measured in the peripheral blood mononuclear cells were significantly lower in “Low mTOR” patients versus that in “High mTOR” while MMP-9 protein expression was significantly higher compared to healthy subjects in both examined OA subsets.

Conclusions Our results show that TIMP1 and MMP-9 gene expressions measured in the peripheral blood might be associated with pain sensitivity in OA outpatients while low level of TIMP1/MMP-9 ratio indicates increased pain perception.

Disclosure of Interest None declared

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