Plasminogen activator inhibitor-1 deficiency enhances subchondral osteopenia after induction of osteoarthritis in mice

Abstract

BackgroundSubchondral osteopenia is important for the pathophysiology of osteoarthritis (OA). Although previous studies suggest that plasminogen activator inhibitor-1 (PAI-1), an inhibitor of fibrinolysis, is related to bone metabolism, its role in OA remains unknown. We therefore investigated the roles of PAI-1 in the subchondral bone in OA model mice.MethodsWild type (WT) and PAI-1-deficient (KO) mice were ovariectomized (OVX), and then destabilization of the medial meniscus (DMM) surgery was performed.ResultsDMM and OVX significantly decreased the trabecular bone mineral density of the subchondral bone evaluated by quantitative computed tomography in PAI-1 KO mice. The effects of OVX and/or PAI-1 deficiency on the OARSI score for the evaluation of the progression of knee degeneration were not significant. PAI-1 deficiency significantly augmented receptor activator nuclear factor κB ligand mRNA levels enhanced by IL-1β in mouse primary osteoblasts, although it did not affect osteoblast differentiation. Moreover, PAI-1 deficiency significantly increased osteoclast formation from mouse bone marrow cells.ConclusionWe showed that PAI-1 deficiency accelerates the subchondral osteopenia after induction of OA in mice. PAI-1 might suppress an enhancement of bone resorption and subsequent subchondral osteopenia after induction of OA in mice.

Serpins in cartilage and osteoarthritis: what do we know?

“…In the future, the use of such mice could inform studies investigating the effect of Serpina1 deficiency in murine experimental arthritis. Fortunately, for most serpins, one human gene is mirrored with a single orthologue in rodents, and indeed transgenic animals have begun to be used successfully to understand the importance of these serpin genes in diseases, including OA [ 61 , 67 , 74 ].…”

“…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 ].…”

The Secretome Derived From Mesenchymal Stromal Cells Cultured in a Xeno-Free Medium Promotes Human Cartilage Recovery in vitro

“…It is related to bone metabolism. Although it has been shown that PAI-1 deficiency accelerates subchondral osteopenia after induction of OA in mice, its role in OA remain unclear (Moritake et al, 2017).…”

Bleeding and bruising in Osteogenesis Imperfecta: International Society on Thrombosis and Haemostasis bleeding assessment tool and haemostasis laboratory assessment in 22 individuals

“…PAI‐1 deficiency has been reported in a patient with OI and spontaneous intraparenchymal haemorrhage (Goddeau et al , ). There is evidence that PAI‐1 also has a role in bone formation in mouse models (Mao et al , ; Moritake et al , ; Jin et al , ). PAI‐1 is stabilized by vitronectin which is anchored to collagen type 1 (Schvartz et al , ).…”