title: [Mechanism of the Piezo1 protein-induced apoptosis of the chondrocytes through the MAPK/ERK1/2 signal pathway].
abstract: OBJECTIVE
  To invstigate the mechanism of new mechanically-activated cation channel protein (Piezo1) can cause the apoptosis of the human chondrocytes under compressive loading, using a Flexercell unit by activating classical Mitogen-activated protein kinase (MAPK) signal pathyway(ERK1/2).
  
  
  METHODS
  Primary human chondrocytes were isolated, cultured, and then subjected to the static compressive loading for 0, 2, 12, 24, 48 h, respectively.The expressions of Piezo1 and the ERK1/2 were assessed by reverse transcription-polymerase chain reaction(PT-PCR), as well as the apoptosis gene B cell lymphoma/leukemia-2(Bcl-2) Bel-associated X protein(Bax). In addition, Piezo1inhibitor, Grammostola spatulata mechanotoxin 4(GsMTx4), was used to block Piezo1, served as a positive control.The immunofluorescence was used to locate the expression of Piezo1 protein and ERK1/2.AnnexinV-PI was used to detect the apoptosis of chondrocytes.
  
  
  RESULTS
  The expression of the Piezo1 in chondrocytesis was weak, the 12 h group was significant increased(0.198 1 vs 0.021 4, P<0.05), the 24 h group was the highest expression while the expression of the 48 h group was lower than the 24 h group, as well as the ERK1/2, Bcl-2 and caspase3.The result of AV-PI had shown that the 2 h group had increased early stage of apoptosis.The 12 h group had increased late stage of apoptosis, and the 24 h group's apoptotic rate was the highest, while the apoptotic rate of the 48 h group was lower than the 24 h group(0.497 1 vs 0.743 1, q=0.035 9). The GsMTx4 could inhibit the late stage of apoptosis, and the location of the Piezo1 was expressed in the nucleus and cytoplasm of the chondrocytes.
  
  
  CONCLUSIONS
  Piezo1 plays an important role in the apoptosis of the human chondrocyte through the classic MAPK/ERK1/2 signal pathway.
authors: Department of Joint Surgery, the Affiliated Hospital of Qingdao University, Qingdao 266000, China.
authors: X F
authors: XF
authors: Li
authors: Z
authors: Z
authors: Zhang
authors: X D
authors: XD
authors: Li
authors: T B
authors: TB
authors: Wang
authors: H N
authors: HN
authors: Zhang
mesh_terms: D017209:Apoptosis; D053148:Caspase 3; D019902:Chondrocytes; D006801:Humans; D007473:Ion Channels; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1
chemical_list: D007473:Ion Channels; C515204:PIEZO1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; C505407:CASP3 protein, human; D053148:Caspase 3