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- Title
Sonic Hedgehog Promotes Cementoblastic Differentiation via Activating the BMP Pathways.
- Authors
Bae, Won-Jung; Auh, Q-Schick; Lim, Hyun-Chang; Kim, Gyu-Tae; Kim, Hyun-Soo; Kim, Eun-Cheol
- Abstract
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.
- Subjects
BONE morphogenetic proteins; CELL differentiation; EMBRYOLOGY; MORPHOGENESIS; RECOMBINANT proteins; PERIODONTAL ligament; CELL proliferation; OSTEOBLASTS; PROTEIN metabolism; ANIMAL experimentation; CELL physiology; CELLS; CELLULAR signal transduction; CEMENTUM; GENES; MICE; PERIODONTIUM; STEM cells
- Publication
Calcified Tissue International, 2016, Vol 99, Issue 4, p396
- ISSN
0171-967X
- Publication type
journal article
- DOI
10.1007/s00223-016-0155-1