Fei He1, Qingshu Li2, Bo Sheng3, Haitao Yang3, Wei Jiang1. 1. Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. 2. Department of Pathology, Chongqing Medical University, Chongqing 400010, China. 3. Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Abstract
BACKGROUND: The application of biomolecular interventions in the early stage of intervertebral disc degeneration (IVDD) is considered an ideal method for the treatment of IVDD. However, the precise definition of the "early stage" of IVDD is unclear. Silent information regulation 2 homologue-1 (SIRT1) can protect human degenerative nucleus pulposus (NP) cells from apoptosis by activating autophagy. However, the mechanism of this effect is still unclear. This study tried to confirm the "early stage" of IVDD and the role of NP cell autophagy during IVDD as well as to determine the mechanism by which SIRT1 protects NP cells. METHODS: The characteristics of the NP in various stages of degeneration were assessed to confirm the "early stage" of IVDD. Then, autophagy and apoptosis were detected in NP cells after SIRT1 upregulation/downregulation. Finally, LY294002 and PD98059 were used to inhibit the AKT/ERK pathway to determine the mechanism by which SIRT1 regulates autophagy in NP cells. RESULTS: Our data showed that mildly degenerative (Pfirrmann grade III with normal height of intervertebral disc) NP cells may be the key target for biomolecular interventions in IVDD and that SIRT1 protects human mildly degenerative NP cells from apoptosis by activating autophagy via the ERK signalling pathway. CONCLUSION: Our data showed that SIRT1 inhibits apoptosis by promoting the autophagic flux in NP cells via the ERK signalling pathway during the key stage of degeneration. These findings will assist in the development of novel therapeutic approaches for IVDD treatment.
BACKGROUND: The application of biomolecular interventions in the early stage of intervertebral disc degeneration (IVDD) is considered an ideal method for the treatment of IVDD. However, the precise definition of the "early stage" of IVDD is unclear. Silent information regulation 2 homologue-1 (SIRT1) can protect human degenerative nucleus pulposus (NP) cells from apoptosis by activating autophagy. However, the mechanism of this effect is still unclear. This study tried to confirm the "early stage" of IVDD and the role of NP cell autophagy during IVDD as well as to determine the mechanism by which SIRT1 protects NP cells. METHODS: The characteristics of the NP in various stages of degeneration were assessed to confirm the "early stage" of IVDD. Then, autophagy and apoptosis were detected in NP cells after SIRT1 upregulation/downregulation. Finally, LY294002 and PD98059 were used to inhibit the AKT/ERK pathway to determine the mechanism by which SIRT1 regulates autophagy in NP cells. RESULTS: Our data showed that mildly degenerative (Pfirrmann grade III with normal height of intervertebral disc) NP cells may be the key target for biomolecular interventions in IVDD and that SIRT1 protects human mildly degenerative NP cells from apoptosis by activating autophagy via the ERK signalling pathway. CONCLUSION: Our data showed that SIRT1 inhibits apoptosis by promoting the autophagic flux in NP cells via the ERK signalling pathway during the key stage of degeneration. These findings will assist in the development of novel therapeutic approaches for IVDD treatment.
Authors: Dirk Beher; John Wu; Suzanne Cumine; Ki Won Kim; Shu-Chen Lu; Larissa Atangan; Minghan Wang Journal: Chem Biol Drug Des Date: 2009-10-20 Impact factor: 2.817
Authors: Yu Moriguchi; Marjan Alimi; Thamina Khair; George Manolarakis; Connor Berlin; Lawrence J Bonassar; Roger Härtl Journal: Global Spine J Date: 2016-01-27