Inhibition of SHH signaling pathway: molecular treatment strategy of odontogenic keratocyst.
Odontogenic keratocyst (OKC) is a relatively common cystic lesion occurred in the tooth-bearing areas of the jaws. This entity is thought to arise from the dental lamina or its remnant with significant growth capacity and recurrence potential. The Sonic hedgehog (SHH) signaling pathway plays a critical role in tooth development. Patched (PTCH) combines with Smoothened (SMO) to form a receptor complex for SHH ligand. Mutations in the PTCH resulting in aberrant activation of SHH signaling pathway were identified as the underlying genetic event of both sporadic and syndrome-related OKCs. We postulate that any strategy to develop antagonists of active receptor, transcriptional factors of SHH signaling pathway will be an effective treatment for OKC. These strategies include reintroducing a wild-type form of PTCH, inhibition of the SMO molecule by synthetic small antagonists and suppression of the downstream transcription factors of the SHH signaling pathway. It seems that inhibition of SMO by intracystic injection of antagonist protein of SMO is the most potential treatment choice.
Zhang
Lu
L
Key Laboratory for Oral Biomedical Engineering of Ministry of Education, School and Hospital of Stomatology, Wuhan University, 237# Luo Yu Road, Wuhan, Hubei, China.
Sun
Zhi-Jun
ZJ
Zhao
Yi-Fang
YF
Bian
Zhuan
Z
Fan
Ming-Wen
MW
Chen
Zhi
Z
D002280:Basal Cell Carcinoma / Q000209:etiology; D002455:Cell Division; D053823:Hedgehog Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007568:Jaw / Q000473:pathology / Q000503:physiopathology; D009154:Mutation; D009807:Odontogenic Cysts / Q000235:genetics / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D012008:Recurrence; D015398:Signal Transduction
D053823:Hedgehog Proteins; C509239:SHH protein, human