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IGF/IGFBP axis in cartilage and bone in osteoarthritis pathogenesis
J Martel-Pelletier1, J A Di Battista, D Lajeunesse
1Osteoarthritis Research Unit, Centre de Recherche L.-C. Simard, CHUM, Montréal, Québec, Canada.
Summary
Osteoarthritis (OA) cartilage shows increased insulin-like growth factor-1 (IGF-1) but reduced chondrocyte response, linked to elevated IGF-binding proteins (IGFBP). Dysregulation of IGFBP-3 and -4 is key in arthritic disorders.
Area of Science:
- Joint biology
- Endocrinology
- Biochemistry
Background:
- Insulin-like growth factor-1 (IGF-1) regulates cartilage matrix anabolism.
- Its effects are controlled by growth factor levels, receptor availability, and binding proteins.
- Disturbances in the IGF system can disrupt joint tissue integrity.
Purpose of the Study:
- To review recent studies on the IGF system in osteoarthritis (OA).
- To explore the relevance of IGF system alterations in OA pathophysiology.
Main Methods:
- Literature review of studies on the IGF system and OA.
- Analysis of IGF-1 expression, receptor interactions, and IGF-binding proteins (IGFBP) in OA tissues.
- Investigation of proteolytic activity against IGFBP in cartilage and bone.
Main Results:
- OA cartilage exhibits increased IGF-1 expression and synthesis.
- Chondrocytes in OA are hyporesponsive to IGF-1, partly due to elevated IGFBP levels.
- IGFBP-3 and IGFBP-4 dysregulation is implicated in arthritic disorders.
- Proteolytic activity against IGFBP is present in cartilage and bone.
- IGF-1 produced by subchondral bone may contribute to OA pathophysiology.
Conclusions:
- Elevated IGFBP levels contribute to chondrocyte hyporesponsiveness in OA.
- Aberrant regulation of the IGF-I/IGFBP system, potentially involving PA/plasmin, may drive subchondral bone changes in OA.
- Understanding the IGF system's role is crucial for OA therapeutic strategies.