GDF-5 and bFGF Activate Matrix Synthesis and Integrin 2-mediated Cell Migration in Ligament Cells

INTRODUCTION: Anterior cruciate ligament (ACL) and medial collateral ligament (MCL) are the major stabilizers of knee joint. The deficiency of these ligaments could result in the early development of osteoarthritis. The cellular activities responding to growth factors have important roles in ligament healings. ACL has a poor healing potential rather than MCL after injuries. To accelerate the ligament healing, we systematically investigated the proliferation, migration, adhesion, and matrix synthesis responding to several growth factors in ACL and MCL cells. Cellular responses including proliferation and migration depend on the interaction between adhesion molecule and extracellular matrix (ECM). Integrins consisting of and subunits primarily mediate cell adhesion by recognizing ECM substrates and cell surface proteins. Adhesion strengths on type I and III collagens, the major components of ligaments, are different in ACL and MCL cells. However, the cellular responses on type I collagen are still unclear in ligament cells. Here, we analyzed the integrin 2, which is the major subunit recognizing type I collagen, -mediated cellular behavior in ACL and MCL cells. In the present study, we demonstrate that basic fibroblast growth factor (bFGF) and growth and differentiation factor (GDF)-5 strongly enhance cell migration and collagen synthesis in ligament cells, respectively.