Matrix Metalloproteinases and Their Inhibitors and Proteoglycan 4 in Patients Undergoing Total Joint Arthroplasty

Abstract

Osteoarthritis, a degenerative disease of the joints, is the most common form of arthritis in the knee. Total joint arthoplasty is a commonly used treatment for joint degeneration and osteoarthritis, and due to these factors, TJA for hip and knee joints is projected to grow by 137% and 601% between 2005 and 2030. Matrix metalloproteases are enzymes found in the extracellular matrix that cleave matrix components. Normally MMPs are downregulated in tissues by Tissue Inhibitors of Metalloproteases, or TIMPs. The relative concentration of TIMPs also may denote some of the activity of the MMPs found in serum. Lubricin (proteoglycan 4) is a molecule found in the synovial fluid that protects joints by dissipating strain energy during locomotion. Lubricin synovial fluid concentration is also diminished in many patients with osteoarthritis, but not all. Given the importance of these three sets of molecules, our lab investigated the correlation between circulating lubricin, MMP levels and TIMPs levels. Blood plasma samples were obtained from de-identified subjects undergoing total joint arthroplasty at Loyola University Medical Center and the University of Utah. Normal blood plasma from pooled healthy individuals served as a control. We analyzed biomarker levels in plasma using ELISA. Our data show that MMP-1 and 9 were increased in TJA patients compared to normal controls, while MMP-2 and 13 were decreased. We also found decreased lubricin and tissue factor in surgical patients relative to controls. These data support the idea that lubricin is vital in protecting the synovial joint and that MMPs play a complex role in the destruction of the joint.

Tissue‐inhibitors of metalloproteinase‐1 and vascular‐endothelial growth‐factor in severe haemophilia A children on low dose prophylactic recombinant factor VIII: Relation to subclinical arthropathy

“…They found that TIMP‐1 was associated with clinical symptoms and radiographic features of OA. Similarly, Thorson et al, 17 found increased level of TIMP‐1 in people with OA than normal people although not statistically significant. These results suggest that macrophage and neutrophil activation lead to elevated TIMP‐1 and MMP‐3 with subsequent cartilage destruction.…”

Proteoglycan 4 Reduces Neuroinflammation and Protects the Blood–Brain Barrier after Traumatic Brain Injury

“…3D). Plasma concentrations of PRG4 measured by ELISA were as low as *100 ng/mL (*1 order of magnitude lower than the reported normal plasma concentration of PRG4), 51 and this value is an overestimation of the actual levels of intact PRG4 given that the ELISA used could not distinguish an intact PRG4 from its degradation products.…”

“…Using the in vitro model of the BBB, we showed that PRG4 can enter the brain through a high-capacity, saturable transport system. Our data indicate that this transport mechanism could easily cope with both physiological (∼2 μg/mL) 51 and potentially therapeutic concentrations of PRG4 in plasma (in rats, plasma levels of rhPRG4 decayed from ∼200 μg/mL down to ∼20 μg/mL within 40 min after its i.v. injection at 3 mg/kg).…”

Acteoside counteracts interleukin-1β-induced catabolic processes through the modulation of mitogen-activated protein kinases and the NFκB cellular signaling pathway

“…Elevated cartilage degrading enzymes including MMP-1, MMP-3, MMP-13, ADMATS-4, and ADAMTS-5 in the synovial uid of patients with OA are the key enzymes responsible for the progressive degeneration of articular cartilage through degradation of collagen and ECM component [26,27]. Hence, the inhibition of MMPs expression and activation seems to be an attractive therapeutic strategy to prevent and attenuate the progressive degeneration of articular cartilage for maintaining the mechanical function of synovial joints [26].…”