Wnt-5a is involved in TGF-beta3-stimulated chondrogenic differentiation of chick wing bud mesenchymal cells.
In this study we investigated whether signalling by TGF-beta3 and Wnt-5a cross-talk during chondrogenic differentiation of chick wing mesenchyme. Using differential display polymerase chain reaction screening, we found the expression of Wnt-5a to be significantly increased during transforming growth factor-beta3 (TGF-beta3)-induced precartilage condensation in mesenchyme micromass cultures. Transfection of cells with a Wnt-5a expression construct promoted precartilage condensation and chondrogenesis in micromass cultures, similar to that observed when chondrogenic-competent cells were exposed to TGF-beta3. Overexpression of Wnt-5a or treatment with TGF-beta3 stimulated the activation of protein kinase C-alpha (PKC-alpha) and p38 mitogen-activated protein kinase (MAPK), both positive regulators of chondrogenic differentiation. Inactivation of PKC-alpha and p38 MAPK by specific inhibitors abrogated chondrogenesis stimulated by both TGF-beta3 and Wnt-5a. Similarly, partial reduction in TGF-beta3-induced Wnt-5a expression by small interfering RNA resulted in decreased activities of PKC-alpha and p38 MAPK, and abolished the chondro-stimulatory effect of TGF-beta3. Collectively, these findings indicate that Wnt-5a, a non-canonical Wnt, can mediate the chondro-stimulatory effect of TGF-beta3 through upregulation of PKC-alpha and p38MAPK signaling.
Jin
Eun-Jung
EJ
Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea.
Park
Jae-Han
JH
Lee
Sun-Young
SY
Chun
Jang-Soo
JS
Bang
Ok-Sun
OS
Kang
Shin-Sung
SS
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo; D020219:Chondrogenesis / Q000502:physiology*; D004628:Embryonic Structures / Q000166:cytology / Q000502:physiology; D004789:Enzyme Activation; D017403:In Situ Hybridization; D008648:Mesoderm / Q000166:cytology / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051571:Protein Kinase C-alpha / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053782:Transforming Growth Factor beta3; D014921:Wings, Animal / Q000166:cytology / Q000254:growth & development*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D020033:Protein Isoforms; D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta; D053782:Transforming Growth Factor beta3; D051153:Wnt Proteins; D051571:Protein Kinase C-alpha; D048051:p38 Mitogen-Activated Protein Kinases