title: Insulin-Like Growth Factor 1 Activates PI3k/Akt Signaling to Antagonize Lumbar Disc Degeneration.
abstract: OBJECTIVE
  The pathogenesis of Lumbar disc degeneration (LDD) has been extensively studied in the past. In particular, a role of matrix metalloproteinase 3 (MMP3) in the disease initiation and progression has been recently reported. However, an involvement of Insulin-like growth factor 1 (IGF-I)-stimulated phosphatidylinositol-3 kinase (PI3k) / Akt signaling pathway-mediated control of MMP3 in LDD has not been acknowledged.
  
  
  METHODS
  We examined the serum IGF-1 levels and activation of the receptor for IGF-1 (IGF-1R) in resected discs in patients with LDD, compared to the fractured discs from traumatized, non-LDD subjects as a control. We analyzed the effects of IGF-1 on the activation of IGF-1R, Akt and MMP3 in a human nucleus pulposus SV40 cell line (HNPSV). We transfected HNPSV cells with a constitutive nuclear FoxO1, and analyzed its effect on the activation of IGF-1R, Akt and MMP3.
  
  
  RESULTS
  LDD patients had significantly lower levels of serum IGF-1, and LDD discs had significantly lower levels of activated IGF-1R. IGF-1 induced phosphorylation of IGF-1R, and then phosphorylation of its downstream factor Akt in the HNPSV cells, resulting in significantly inhibition of MMP3. Further, FoxO1 nuclear retention completely abolished the inhibitory effects of IGF-1 on MMP3 in HNPSV cells.
  
  
  CONCLUSIONS
  Together, IGF-1/Akt/FoxO1/MMP3 regulatory machinery may control the development of LDD.
authors: Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, China.
authors: Zuoqing
authors: Z
authors: Liu
authors: Kaihua
authors: K
authors: Zhou
authors: Wenqin
authors: W
authors: Fu
authors: Hailong
authors: H
authors: Zhang
mesh_terms: D002460:Cell Line; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D055959:Intervertebral Disc Degeneration / Q000378:metabolism*; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; D019278:Matrix Metalloproteinase 3