Table 1.
Role of Wnt signaling during early stages of cartilage development.
| Promoting Effects | |
| Wnt5a | Expressed in perichondrium surrounding condensations Recruits mesenchymal stem cells Delays chondrocyte differentiation |
| Wnt5b | Expressed in pre-hypertrophic chondrocytes and in the perichondrium Promotes initial steps of chondrogenesis in micromass cultures by stimulating cartilage nodule formation Delays terminal differentiation in vivo |
| β-catenin low level | Expressed in chondrogenic mesenchymal condensations Induces expression of Sox9 and promotes chondrogenic differentiation |
| Dkk1sFRP1 | Promotes early chondrogenesis in human mesenchymal stem cells |
| Wif-1 | Expressed in mesenchyme surrounding cartilage elements and articular cartilage Promotes chondrogenic differentiation by neutralizing Wnt3a mediated inhibition of chondrogenesis |
| Inhibitory Effects | |
| Wnt1 | Inhibits cell condensation and thus cartilage formation |
| Wnt3a | Expressed in early stages of chondrogenesis, decreased when chondrogenic differentiation proceeds Increases self-renewal and decreases apoptosis of MSCs Stabilizes cell-cell adhesion through promoting sustained expression of N-cadherin and β-catenin Blocks collagen II expression and proteoglycan deposition |
| Wnt4 | Expressed in developing joint interzone Inhibits cell condensation and thus chondrogenesis condensation |
| Wnt6 | Inhibits chondrogenesis at an early stage prior to chondrogenic differentiation (up-stream of SOX-9) |
| Wnt7a | Expressed in dorsal ectoderm in developing limb Inhibits chondrogenic differentiation in vitro and in vivo mediated by MAPK and AP-1 signaling Prolongs stabilization of N-cadherin Blocks transition from the condensation state to the cartilaginous nodule formation |
| Wnt9a (14) | Expressed in developing joint interzone Expressed in synovium and joint capsule in the mature joint Arrests or reverses chondrogenic differentiation Blocks transition from the condensation state to the cartilaginous nodule formation |
| Fzl7 | Inhibits mesenchymal condensation at the pre-cartilage aggregate formation by suppressing N-cadherin expression |