Signaling factor | Effects on growth plate chondrocytes | Role in OA |
---|---|---|
Bone morphogenic proteins | Induce proliferation | Stimulation of MMP-13 |
 | Inhibit hypertrophy |  |
Fibroblast growth factors | Decrease proliferation | Stimulation of ADAMTS-5 |
 | Decrease hypertrophy |  |
 | Decrease matrix production |  |
TGFβ | Variable effects depending on species and concentration | Stimulation of MMP-13 |
Wnt/β-catenin | Positive regulator of hypertrophy and ossification | Activation of maturational genes |
 |  | Induction of matrix degradation |
 |  | Induction of MMPs and aggrecanases mediated by WISP-1 |
Indian hedgehog | Stimulates proliferation | Induction of ADAMTS-5 via Runx2 |
 | Inhibits hypertrophy via parathyroid hormone-related peptide |  |
 | Directly induces hypertrophy in vitro |  |
Retinoic acid | Positive regulator of hypertrophy and matrix mineralization | Induction of MMP-13 and aggrecanases |
Growth hormone/IGF-I | Stimulate proliferation | Growth hormone is a beneficial factor in OA |
 | Initiate hypertrophy | IGF-I signaling is antagonized by IGF-binding proteins |
Collagen IX | Stimulates chondrocyte proliferation | Essential for tissue integrity, loss of collagen IX induces OA |
 | Essential for columnar organization of growth plate chondrocytes |  |
β1 integrins | Mediate adhesion to surrounding matrix and motility | Essential for normal knee joint development |
 | Essential for proliferation | Minor influence on cartilage homeostasis |
Discoidin domain receptors | Regulate cell proliferation, adhesion and motility | Induction of MMP-13 and MMP-derived type II collagen Fragments |
 | Control matrix remodeling |  |
MMPs/ADAMTSs | Essential for matrix remodeling | Key factors in matrix degradation during OA |
 | Influence bioavailability of VEGF | Matrix degradation is accompanied by terminal chondrocyte differentiation, positive feedback mechanism? |
Sox 9 | Regulate proliferation and hypertrophic differentiation | Involved in MMP-13 expression |
Runx2/3 | Positive regulation of chondrocyte hypertrophy | Induction of chondrocyte hypertrophy |
 | Influence on angiogenesis by up regulation of VEGF | Induction of MMP-13 expression |
CCAAT/enhancer binding | Inhibition of proliferation | Mediates cartilage destruction protein beta |
 | Stimulation of hypertrophy |  |
 | Activation of collagen X expression |  |