title: Involvement of PI3K/Akt pathway in rat condylar chondrocytes regulated by PTHrP treatment.
abstract: OBJECTIVE
  The aim of this study was to explore the mutual communication of the parathyroid hormone-related peptide (PTHrP) and phosphatidylinositol 3-kinase/threonine protein kinase (PI3K/Akt) pathway on the proliferation and differentiation of condylar chondrocytes from Sprague-Dawley (SD) rats.
  
  
  METHODS
  Condylar chondrocytes from the condylar cartilage were cultured and an organ culture system of mandibular condyles was employed. The distribution of PI3K, phospho-Akt (p-Akt), and PTHrP in condylar cartilage was detected by either immunohistochemistry or immunofluorescence. The second passage chondrocytes and condyle specimens in the organ culture system were treated with PTHrP, LY294002, PTHrP and LY294002 in combination, or dimethyl sulfoxide (DMSO), separately. The mRNA and protein levels of type II (Col II) and type X collagen (Col X) were investigated by real-time polymerase chain reaction (PCR) and Western blot analysis. The condyle growth in organ culture system was analysed by haematoxylin-eosin staining.
  
  
  RESULTS
  PTHrP, PI3K, and p-Akt were mainly located in the proliferative and hypertrophic zones. PTHrP promoted the proliferation of condylar chondrocytes, while LY294002 limited this effect. The mRNA and protein levels of Col II and Col X in these cells were reduced by PTHrP and enhanced by LY294002. Organ culture showed a significant enhancement of condyle elongation with PTHrP treatment or a combination of PTHrP and LY294002 treatment. After treatment with LY294002, the length of condyles was reduced compared with the samples treated with DMSO.
  
  
  CONCLUSIONS
  We conclude that the PI3K/Akt pathway plays an essential role in the proliferation and differentiation of condylar chondrocytes and is a potential target for PTHrP in regulating chondrocyte differentiation at condylar cartilage.
authors: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; Wenzhou Medical University, Wenzhou 325027, China.
authors: Zhennan
authors: Z
authors: Deng
authors: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
authors: Yang
authors: Y
authors: Liu
authors: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
authors: Chaopeng
authors: C
authors: Wang
authors: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
authors: Hongyi
authors: H
authors: Fan
authors: Wenzhou Medical University, Wenzhou 325027, China.
authors: Jianfeng
authors: J
authors: Ma
authors: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China. Electronic address: yhyang6812@scu.edu.cn.
authors: Haiyang
authors: H
authors: Yu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002356:Cartilage / Q000187:drug effects; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000201:enzymology*; D002867:Chromones / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D008335:Mandibular Condyle / Q000166:cytology*; D009025:Morpholines / Q000494:pharmacology; D044162:Parathyroid Hormone-Related Protein / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002867:Chromones; D009025:Morpholines; D044162:Parathyroid Hormone-Related Protein; D012333:RNA, Messenger; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D004121:Dimethyl Sulfoxide
keywords: Chondrocytes; Condylar cartilage; PI3K/Akt pathway; Parathyroid hormone-related peptide (PTHrP)