Fibrinolytic Mechanisms in Bone Repair
Summary
Bone injury initiates a cascade of events in which deposition of a fibrin-rich matrix at the lesion site provides a provisional scaffold for cell adhesion and migration. Fibrinolytic mechanisms, centred on the plasminogen/plasmin system, orchestrate the timely degradation of this matrix, thereby promoting clearance of debris, mobilisation of stem and progenitor cells, and release of growth factors that drive angiogenesis and osteogenesis. Urokinase-type and tissue-type plasminogen activators, expressed by osteoblasts, osteoclasts and infiltrating immune cells, locally convert plasminogen to plasmin, which in turn degrades fibrin and activates matrix metalloproteinases. This proteolytic network regulates the balance between bone resorption and formation, influences the differentiation and activity of osteoclasts and osteoblasts, and interlinks coagulation, inflammation and tissue regeneration. Modulation of plasminogen activator inhibitor-1 levels fine-tunes this process: excessive inhibition of fibrinolysis can impair matrix remodelling and delay healing, while insufficient control may lead to pathological bone loss. Collectively, fibrinolytic pathways constitute a critical component of the bone repair programme, mediating matrix turnover, cellular recruitment and growth factor availability to ensure restoration of skeletal integrity.
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Fibrinolytic Mechanisms in Bone Repair publication trend
The graph below shows the total number of articles in fibrinolytic mechanisms in bone repair across all publications each year (not limited to Nature Index journals).
Technical terms
Fibrinolysis: The enzymatic process by which fibrin matrices are degraded, facilitating tissue remodelling.
Plasminogen: The inactive precursor of plasmin circulating in blood and tissue.
Plasmin: A serine protease that degrades fibrin and activates matrix remodelling enzymes.
Plasminogen activator: Enzymes such as urokinase-type and tissue-type plasminogen activators that convert plasminogen to plasmin.
Plasminogen Activator Inhibitor-1 (PAI-1): The principal inhibitor of plasminogen activators, regulating fibrinolysis.
Osteoblast: A cell responsible for bone formation through deposition of matrix proteins.
Osteoclast: A multinucleated cell specialised in bone resorption and matrix degradation.
References
- The Roles of Fibrinolytic Factors in Bone Destruction Caused by Inflammation. Cells (2024).
- Plasminogen/Plasmin Modulates Bone Metabolism by Regulating the Osteoblast and Osteoclast Function*. Journal of Biological Chemistry (2011).
- The Deleterious Effects of Impaired Fibrinolysis on Skeletal Development Are Dependent on Fibrin(ogen), but Independent of Interlukin-6. Frontiers in Cardiovascular Medicine (2021).
- Role of Macrophages and Plasminogen Activator Inhibitor-1 in Delayed Bone Repair Induced by Glucocorticoids in Mice. International Journal of Molecular Sciences (2022).
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