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.
Highlights
IntroductionPrevious studies suggest that plasminogen activator inhibitor-1 (PAI-1), an inhibitor of fibrinolysis, is related to bone metabolism, its role in OA remains unknown
Subchondral osteopenia is important for the pathophysiology of osteoarthritis (OA)
Effects of destabilization of the medial meniscus (DMM), OVX and plasminogen activator inhibitor-1 (PAI-1) deficiency on bone mineral density (BMD) of subchondral bone in mice We evaluated the trabecular BMD of the tibial subchondral bone, in which regions of interest (ROI) were defined as 240 μm (10-slice) segments from 72 μm proximal to the end of the proximal growth plate towards the joint using quantitative CT analysis
Summary
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. Changes in bone around the joint, especially the subchondral bone, have recently been suggested to be involved in the disease condition from a relatively early stage in OA. The subchondral bone is influenced by a high bone turnover state. Radin et al suggested that the integrity of the articular cartilage depends on the underlying bone strength [6]. They speculated that cartilage degeneration is prone to progress by load stress in the osteoporotic state of the subchondral bone.
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