TGF-beta2 stimulates cranial suture closure through activation of the Erk-MAPK pathway.
Cranial sutures are important growth sites of the skull. During suture closure, the dura mater is one of the most important sources of various positive and negative regulatory signals. Previous results indicate that TGF-beta2 from dura mater strongly accelerates suture closure, however, its exact regulatory mechanism is still unclear. In this study, we confirmed that removal of dura mater in calvarial organ culture strongly accelerates sagittal suture closure and that this effect is further enhanced by TGF-beta2 treatment. TGF-beta2 stimulated cell proliferation in the MC3T3-E1 cell line. Similarly, it stimulated the proliferation of cells in the sutural space in calvarial organ culture. Furthermore, TGF-beta2-mediated enhanced cell proliferation and suture closure were almost completely inhibited by an Erk-MAPK blocker, PD98059. These results indicate that TGF-beta2-induced activation of Erk-MAPK is an important signaling component that stimulates cell proliferation to enrich osteoprogenitor cells, thereby promoting their differentiation into osteoblasts to achieve a rapid calvarial bone expansion.
Lee
Sang-Won
SW
Department of Pediatric Dentistry, School of Dentistry, Kyungpook National University, Daegu, Korea.
Choi
Kang-Young
KY
Cho
Je-Yoel
JY
Jung
Sung-Hwa
SH
Song
Kun-Bae
KB
Park
Eui-Kyun
EK
Choi
Je-Yong
JY
Shin
Hong-In
HI
Kim
Shin-Yoon
SY
Woo
Kyung-Mi
KM
Baek
Jeong-Hwa
JH
Nam
Soon-Hyeun
SH
Kim
Young-Jin
YJ
Kim
Hyun-Jung
HJ
Ryoo
Hyun-Mo
HM
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D003393:Cranial Sutures / Q000166:cytology / Q000196:embryology*; D004388:Dura Mater / Q000166:cytology / Q000196:embryology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D009924:Organ Culture Techniques; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology; D053781:Transforming Growth Factor beta2
C509041:TGFB2 protein, human; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D048049:Extracellular Signal-Regulated MAP Kinases