Plasminogen activator inhibitor-1 is involved in interleukin-1β-induced matrix metalloproteinase expression in murine chondrocytes

Moritake, Akihiro; Kawao, Naoyuki; Okada, Kiyotaka; Ishida, Masaharu; Tatsumi, Kohei; Matsuo, Osamu; Akagi, Masao; Kaji, Hiroshi

doi:10.1080/14397595.2018.1525018

Cited by 3 publications

(2 citation statements)

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“…Neither study investigates the involvement of serine proteinases in these observations, and it is possible that SerpinE2 may have chondroprotective roles outside of proteinase inhibition. Interestingly, an inverse observation has been made for SerpinE1, as murine chondrocytes from SerpinE1 −/− mice show a reduction in IL-1 induced Mmp13 expression [ 60 ]. These mice also display accelerated subchondral osteopenia compared with wild-type mice following surgical induction of OA in ovariectomized female mice [ 61 ].…”

Section: Serpins In Cartilage and Osteoarthritismentioning

confidence: 99%

Serpins in cartilage and osteoarthritis: what do we know?

Wilkinson

2021

Biochemical Society Transactions

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Serpins (serine proteinase inhibitors) are an ancient superfamily of structurally similar proteins, the majority of which use an elegant suicide inhibition mechanism to target serine proteinases. Despite likely evolving from a single common ancestor, the 36 human serpins have established roles regulating diverse biological processes, such as blood coagulation, embryonic development and extracellular matrix (ECM) turnover. Genetic mutations in serpin genes underpin a host of monogenic disorders — collectively termed the ‘serpinopathies’ — but serpin dysregulation has also been shown to drive pathological mechanisms in many common diseases. Osteoarthritis is a degenerative joint disorder, characterised by the progressive destruction of articular cartilage. This breakdown of the cartilage is driven by the metalloproteinases, and it has long been established that an imbalance of metalloproteinases to their inhibitors is of critical importance. More recently, a role for serine proteinases in cartilage destruction is emerging; including the activation of latent matrix metalloproteinases and cell-surface receptors, or direct proteolysis of the ECM. Serpins likely regulate these processes, as well as having roles beyond serine proteinase inhibition. Indeed, serpins are routinely observed to be highly modulated in osteoarthritic tissues and fluids by ‘omic analysis, but despite this, they are largely ignored. Confusing nomenclature and an underappreciation for the role of serine proteinases in osteoarthritis (OA) being the likely causes. In this narrative review, serpin structure, biochemistry and nomenclature are introduced, and for the first time, their putative importance in maintaining joint tissues — as well as their dysregulation in OA — are explored.

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Section: Serpins In Cartilage and Osteoarthritismentioning

confidence: 99%

Serpins in cartilage and osteoarthritis: what do we know?

Wilkinson

2021

Biochemical Society Transactions

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show abstract

“… 35 Conversely, an excess of PAI-1 has also been associated with cartilage damage in OA because it increases the numbers of metalloproteinases. 36 …”

Section: Discussionmentioning

confidence: 99%