Table 1.
The effect of activation of the canonical and non-canonical signalling pathways with prominent roles in bone homeostasis. Only studies where the involved signalling pathway was confirmed are included.
| Ligand | Effects of Activation of Non-Canonical | Non-Canonical Signal Transduction |
Effects of Activation of Canonical |
|---|---|---|---|
| Wnt1 | N/A | Stem cell maintenance [56] | |
| Promotion of Osteoblastogenesis [56,57] | |||
| Wnt2b | N/A | Osteogenic differentiation [58,59] | |
| Wnt3a | Suppression of osteoclast differentiation | cAMP/PKA pathway [60] | Stem cell maintenance [36,61,62,63] |
| Suppression of chondrocyte differentiation | c-Jun/AP-1 [60] | Suppression of osteoblastogenesis [64,65] | |
| Induction of osteoblastogenesis | PKCδ [66] | Suppression of osteoclastogenesis [60,67] | |
| mTORC1, mTORC2 [68,69] | Suppression of chondrogenesis [70] | ||
| JNK pathway [31] | |||
| Promotion of osteoblastogenesis | RhoA [71] | ||
| Prevention of starvation induced apoptosis | c-Src/ERK1/2 and PI3K/Akt [32] | ||
| Wnt4 | Osteogenic differentiation, bone formation | p38 MAPK [72] | N/A |
| Inhibition of osteoclast differentiation | TAK1-TAB2-NLK [73] | ||
| Wnt5a | Promotion of osteoclastogenesis | DAAM2/Rho/PKN3/c-Src [74] | N/A |
| JNK/c-Jun/Sp1 [19] | |||
| PKC/CAMKIIα/JNK [64] | |||
| Suppression of canonical Wnt signalling | PKC/CAMKIIα/JNK [64] | ||
| TAK1/NLK [75] | |||
| Prevention of starvation-induced apoptosis | c-Src/ERK1/2 and PI3K/Akt [32] | ||
| Promotion of chondrogenesis | CaMK/NFAT [76] | ||
| Inhibition of chondrogenesis | PI3K/Akt/IKK/NF-κB [76] | ||
| Promotion of osteoblastogenesis | RhoA [77] | ||
| JNK/c-Jun [78] | |||
| Wnt5b | Suppression of chondrogenesis | JNK pathway [79] | N/A |
| Wnt7b | Promotion of osteoblastogenesis | mTORC1, mTORC2 [69,80] | N/A |
| Gαq/11/PLCβ/PKCδ [66] | |||
| Wnt10b | Promotion of osteoblastogenesis | mTORC2 [69] | Promotion of osteoblastogenesis [81,82,83,84,85,86] |
| Wnt16 | Suppression of osteoclastogenesis | JNK/c-Jun [86] | Suppression of osteoclastogenesis [87] |
| Promotion of osteogenesis | JNK pathway [65] |
Abbreviations: Akt: protein kinase B; AP-1: activator protein 1; CAMK: calcium/calmodulin-dependent protein kinase; cAMP: cyclic adenosine monophosphate; c-Jun: Jun Proto-Oncogene, AP-1 transcription factor subunit; c-Src: SRC non-receptor tyrosine kinase; DAAM2: dishevelled associated activator of morphogenesis 2; ERK: extracellular signal-regulated kinase; IKK: inhibitor of nuclear factor-κB (IκB) kinase; JNK: c-Jun N-terminal kinase; MAPK: mitogen-activated protein kinase; mTORC: mechanistic target of rapamycin complex; NFAT: nuclear factor of activated T cells; NF-κB: nuclear factor κB; NLK: Serine/threonine-protein kinase NLK; PI3K: phosphatidylinositol 3-kinase; PLC: phospholipase C; PKA: protein kinase A; PKCδ: protein kinase C delta; PKN3: protein kinase N3; RhoA: Ras homolog family member A; TAB2: TGF-beta-activated kinase 1; TAK1: TGF-β–activated kinase 1.