Sonic Hedgehog Promotes Cementoblastic Differentiation via Activating the BMP Pathways.
Although sonic hedgehog (SHH), an essential molecule in embryogenesis and organogenesis, stimulates proliferation of human periodontal ligament (PDL) stem cells, the effects of recombinant human SHH (rh-SHH) on osteoblastic differentiation are unclear. To reveal the role of SHH in periodontal regeneration, expression of SHH in mouse periodontal tissues and its effects on the osteoblastic/cementoblastic differentiation in human cementoblasts were investigated. SHH is immunolocalized to differentiating cementoblasts, PDL cells, and osteoblasts of the developing mouse periodontium. Addition of rh-SHH increased cell growth, ALP activity, and mineralization nodule formation, and upregulated mRNA expression of osteoblastic and cementoblastic markers. The osteoblastic/cementoblastic differentiation of rh-SHH was abolished by the SHH inhibitor cyclopamine (Cy) and the BMP antagonist noggin. rh-SHH increased the expression of BMP-2 and -4 mRNA, as well as levels of phosphorylated Akt, ERK, p38, and JNK, and of MAPK and NF-κB activation, which were reversed by noggin, Cy, and BMP-2 siRNA. Collectively, this study is the first to demonstrate that SHH can promote cell growth and cell osteoblastic/cementoblastic differentiation via BMP pathway. Thus, SHH plays important roles in the development of periodontal tissue, and might represent a new therapeutic target for periodontitis and periodontal regeneration.
Department of Oral and Maxillofacial Pathology, School of Dentistry and Research Center for Tooth & Periodontal Regeneration (MRC), Kyung Hee University, 14 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02453, Republic of Korea.
Won-Jung
WJ
Bae
Department of Oral Medicine, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
Q-Schick
QS
Auh
Department of Periodontology, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
Hyun-Chang
HC
Lim
Department of Oral and Maxillofacial Radiology, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
Gyu-Tae
GT
Kim
Department of Orthodontics, Graduate School, Kyung Hee University, Seoul, Republic of Korea.
Hyun-Soo
HS
Kim
Department of Oral and Maxillofacial Pathology, School of Dentistry and Research Center for Tooth & Periodontal Regeneration (MRC), Kyung Hee University, 14 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02453, Republic of Korea. eckim@khu.ac.kr.
Eun-Cheol
EC
Kim
D016475:3T3 Cells; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D003739:Dental Cementum / Q000166:cytology*; D005260:Female; D005786:Gene Expression Regulation; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D010006:Osteoblasts / Q000166:cytology*; D010513:Periodontal Ligament / Q000378:metabolism; D010519:Periodontium / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology
C525718:BMP2 protein, human; C525809:BMP4 protein, human; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D053823:Hedgehog Proteins; D011994:Recombinant Proteins; C509239:SHH protein, human
Cementoblasts; Differentiation; Signal pathways; Sonic hedgehog