title: Effect of melatonin on the proliferation and differentiation of chondrocytes from rat vertebral body growth plate in vitro.
abstract: OBJECTIVE
  Abnormal growth of vertebral body growth plate (VBGP) is considered as one of the etiologic factors in the adolescent idiopathic scoliosis (AIS). It was well-known that melatonin was correlated with the emergence and development of AIS. This study aimed to investigate the effect of melatonin on rat VBGP chondrocytes in vitro.
  
  
  METHODS
  Chondrocytes were isolated from rat VBGP, and treated with or without melatonin. Cell proliferation was measured by the Alamar Blue assay. Gene expression of collagen type II and aggrecan were evaluated by real-time PCR. Expression of the melatonin receptors (MT1, MT2), proliferating cell nuclear antigen (PCNA, a cell proliferation marker), Sox9 (a chondrocytic differentiation marker) and Smad4 (a common mediator in regulating the proliferation and differentiation of chondrocytes) were detected by Western blotting.
  
  
  RESULTS
  Expression of melatonin receptors (MT1, MT2) were detected in the rat VBGP chondrocytes. Melatonin, at 10 and 100 µg/mL concentration, significantly inhibited the proliferation of VBGP-chondrocytes and the gene expression of collagen type II and aggrecan, and down-regulated the protein expression of PCNA, Sox9 and Smad4. In addition, the inhibitory effect of melatonin was reversed by luzindole, a melatonin receptor antagonist.
  
  
  CONCLUSIONS
  These results suggest that melatonin at high concentrations can inhibit the proliferation and differentiation of VBGP chondrocytes, which might give some new insight into the pathogenic mechanism of AIS.
authors: Department of Spinal Surgery, Nanfang Hospital, Southern Medical University, China.
authors: Zhao-Ming
authors: ZM
authors: Zhong
authors: Tao
authors: T
authors: Li
authors: Zi-Xing
authors: ZX
authors: Xu
authors: Ting-Ting
authors: TT
authors: Meng
authors: Ji-Huan
authors: JH
authors: Zeng
authors: Shuai
authors: S
authors: Zheng
authors: Wen-Bin
authors: WB
authors: Ye
authors: Qian
authors: Q
authors: Wu
authors: Jian-Ting
authors: JT
authors: Chen
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects*; D006132:Growth Plate / Q000166:cytology*; D008550:Melatonin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044122:Receptor, Melatonin, MT1 / Q000378:metabolism; D044123:Receptor, Melatonin, MT2 / Q000378:metabolism
chemical_list: D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D008550:Melatonin
keywords: Smad4.; Sox9; adolescent idiopathic scoliosis; melatonin; proliferating cell nuclear antigen; vertebral body growth plate
references: J Bone Joint Surg Am. 2003 Apr;85(4):715-26
references: 12672851
references: J Bone Joint Surg Br. 1987 Nov;69(5):690-2
references: 3680325
references: Ann Med. 2010 May 6;42(4):276-85
references: 20455793
references: J Pineal Res. 2011 Sep;51(2):187-94
references: 21470302
references: J Biol Chem. 1997 Oct 24;272(43):26918-25
references: 9341126
references: Scoliosis. 2008 Jan 26;3:3
references: 18221547
references: Dev Dyn. 2009 Aug;238(8):1897-908
references: 19582869
references: Urol Res. 2003 Aug;31(4):276-9
references: 12844242
references: Hum Reprod. 2007 May;22(5):1304-9
references: 17307808
references: Eur Spine J. 2011 May;20 Suppl 1:S68-74
references: 21416282
references: J Immunol Methods. 1997 May 26;204(2):205-8
references: 9212838
references: Dev Biol. 2005 Aug 15;284(2):311-22
references: 16023633
references: Bone. 2005 Oct;37(4):530-44
references: 16054883
references: Arthritis Rheum. 1967 Jun;10(3):235-9
references: 4291108
references: Genes Dev. 2004 May 1;18(9):1072-87
references: 15132997
references: Anal Biochem. 1976 May 7;72:248-54
references: 942051
references: J Pineal Res. 2010 Oct;49(3):222-38
references: 20626586
references: J Orthop Res. 1991 May;9(3):348-59
references: 2010838
references: J Bone Joint Surg Am. 1950 Oct;32 A(4):803-14
references: 14784489
references: Genes Dev. 2002 Nov 1;16(21):2813-28
references: 12414734
references: J Bone Miner Res. 1999 Jul;14(7):1145-52
references: 10404014
references: Lancet. 2008 May 3;371(9623):1527-37
references: 18456103
references: J Bone Joint Surg Br. 2003 Sep;85(7):1026-31
references: 14516040
references: J Pineal Res. 2003 Jan;34(1):75-8
references: 12485375
references: J Bone Joint Surg Br. 1997 May;79(3):483-6
references: 9180333
references: Spine (Phila Pa 1976). 1999 Oct 1;24(19):1985-9
references: 10528372
references: Spine (Phila Pa 1976). 1996 May 15;21(10):1140-6
references: 8727187
references: Spine (Phila Pa 1976). 2004 Aug 15;29(16):1772-81
references: 15303021
references: Pediatr Int. 2006 Dec;48(6):591-8
references: 17168980
references: J Bone Joint Surg Br. 1995 Jan;77(1):134-8
references: 7822371
references: Spine (Phila Pa 1976). 2005 Feb 15;30(4):411-7
references: 15706338
references: Spine (Phila Pa 1976). 1998 Jan 1;23(1):41-6
references: 9460151
references: J Bone Joint Surg Br. 2000 Apr;82(3):399-403
references: 10813177
references: J Cell Physiol. 2007 Dec;213(3):635-41
references: 17886256
references: J Pineal Res. 2009 Apr;46(3):344-8
references: 19317797
references: Spine (Phila Pa 1976). 2006 Aug 1;31(17):1933-42
references: 16924210
references: J Biol Chem. 1999 Jul 30;274(31):22041-7
references: 10419530
references: J Pineal Res. 2011 Jan;50(1):8-20
references: 20964709
references: J Biomech. 2009 Aug 25;42(12):1793-803
references: 19540500
references: J Pineal Res. 2009 Aug;47(1):70-4
references: 19538337
references: J Pineal Res. 2009 Mar;46(2):181-7
references: 19054299
references: Spine (Phila Pa 1976). 2003 Sep 15;28(18):2152-7
references: 14501928
references: Clin Orthop Relat Res. 2007 Sep;462:45-52
references: 17563702
references: Spine (Phila Pa 1976). 1996 May 15;21(10):1147-52
references: 8727188
references: Stud Health Technol Inform. 2002;88:3-9
references: 15455995
references: Spine (Phila Pa 1976). 1999 Jan 1;24(1):35-43
references: 9921589