Periodic Mechanical Stress Stimulates Cav-1-Dependent IGF-1R Mitogenic Signals in Rat Chondrocytes Through ERK1/2
Background/Aims: The biological effects of periodic mechanical stress on the mitogenesis of chondrocytes have been studied extensively over the past few years. However, the mechanisms underlying the ability of chondrocytes to sense and respond to mechanical stimuli remain to be determined. In the cu...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Cell Physiol Biochem Press GmbH & Co KG
2018-08-01
|
| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | https://www.karger.com/Article/FullText/492288 |
| _version_ | 1828769450095017984 |
|---|---|
| author | Kewei Ren Jilei Tang Xuefeng Jiang Huiqing Sun Luming Nong Nan Shen Yanqing Gu |
| author_facet | Kewei Ren Jilei Tang Xuefeng Jiang Huiqing Sun Luming Nong Nan Shen Yanqing Gu |
| author_sort | Kewei Ren |
| collection | DOAJ |
| description | Background/Aims: The biological effects of periodic mechanical stress on the mitogenesis of chondrocytes have been studied extensively over the past few years. However, the mechanisms underlying the ability of chondrocytes to sense and respond to mechanical stimuli remain to be determined. In the current study, we analyzed the mechanisms by which periodic mechanical stress is translated into biochemical signals and verified the key role of non-integrin mechanosensors including Caveolin-1 (Cav-1), and insulin-like growth factor-1 receptor (IGF-1R) in chondrocyte proliferation. Methods: Two steps were undertaken in the experiment. In the first step, the cells were maintained under static conditions or periodic mechanical stress for 0 h and 1 h prior to Western blot analysis. In the second step, the cells were pretreated with short hairpin RNA (shRNA) targeted to Cav-1 or IGF-1R or control scrambled shRNA. Moreover, they were pretreated with their selective inhibitors methyl β-cyclodextrin (MCD) or Linsitinib (OSI-906). They were maintained under static conditions or periodic mechanical stress for 1 h prior to Western blot analysis, and for 3 days, 8 h per day, prior to direct cell counting and CCK-8 assay, respectively. Results: Periodic mechanical stress significantly induced sustained phosphorylation of Cav-1 at Tyr14 and IGF-1R at Tyr1135/1136. Proliferation was inhibited by pretreatment with Cav-1 inhibitor MCD and by shRNA targeted to Cav-1 in chondrocytes in response to periodic mechanical stress. Meantime, MCD and shRNA targeted to Cav-1 also attenuated IGF-1R, and extracellular signal-regulated kinase (ERK)1/2 activation. In addition, inhibiting IGF-1R activity by Linsitinib and shRNA targeted to IGF-1R abrogated chondrocyte proliferation and phosphorylation level of ERK1/2 subjected to periodic mechanical stress, while the phosphorylation site of Cav-1 was not affected. Conclusion: These findings collectively suggested that periodic mechanical stress promoted chondrocyte proliferation through Cav-1-IGF-1R-ERK1/2. |
| first_indexed | 2024-12-11T13:48:11Z |
| format | Article |
| id | doaj.art-425d606eef634748817d98d275f2a7fc |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-11T13:48:11Z |
| publishDate | 2018-08-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-425d606eef634748817d98d275f2a7fc2022-12-22T01:04:22ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-08-014841652166310.1159/000492288492288Periodic Mechanical Stress Stimulates Cav-1-Dependent IGF-1R Mitogenic Signals in Rat Chondrocytes Through ERK1/2Kewei RenJilei TangXuefeng JiangHuiqing SunLuming NongNan ShenYanqing GuBackground/Aims: The biological effects of periodic mechanical stress on the mitogenesis of chondrocytes have been studied extensively over the past few years. However, the mechanisms underlying the ability of chondrocytes to sense and respond to mechanical stimuli remain to be determined. In the current study, we analyzed the mechanisms by which periodic mechanical stress is translated into biochemical signals and verified the key role of non-integrin mechanosensors including Caveolin-1 (Cav-1), and insulin-like growth factor-1 receptor (IGF-1R) in chondrocyte proliferation. Methods: Two steps were undertaken in the experiment. In the first step, the cells were maintained under static conditions or periodic mechanical stress for 0 h and 1 h prior to Western blot analysis. In the second step, the cells were pretreated with short hairpin RNA (shRNA) targeted to Cav-1 or IGF-1R or control scrambled shRNA. Moreover, they were pretreated with their selective inhibitors methyl β-cyclodextrin (MCD) or Linsitinib (OSI-906). They were maintained under static conditions or periodic mechanical stress for 1 h prior to Western blot analysis, and for 3 days, 8 h per day, prior to direct cell counting and CCK-8 assay, respectively. Results: Periodic mechanical stress significantly induced sustained phosphorylation of Cav-1 at Tyr14 and IGF-1R at Tyr1135/1136. Proliferation was inhibited by pretreatment with Cav-1 inhibitor MCD and by shRNA targeted to Cav-1 in chondrocytes in response to periodic mechanical stress. Meantime, MCD and shRNA targeted to Cav-1 also attenuated IGF-1R, and extracellular signal-regulated kinase (ERK)1/2 activation. In addition, inhibiting IGF-1R activity by Linsitinib and shRNA targeted to IGF-1R abrogated chondrocyte proliferation and phosphorylation level of ERK1/2 subjected to periodic mechanical stress, while the phosphorylation site of Cav-1 was not affected. Conclusion: These findings collectively suggested that periodic mechanical stress promoted chondrocyte proliferation through Cav-1-IGF-1R-ERK1/2.https://www.karger.com/Article/FullText/492288Periodic mechanical stressChondrocyte proliferationNon-integrin mechanosensorsCav-1IGF-1R |
| spellingShingle | Kewei Ren Jilei Tang Xuefeng Jiang Huiqing Sun Luming Nong Nan Shen Yanqing Gu Periodic Mechanical Stress Stimulates Cav-1-Dependent IGF-1R Mitogenic Signals in Rat Chondrocytes Through ERK1/2 Cellular Physiology and Biochemistry Periodic mechanical stress Chondrocyte proliferation Non-integrin mechanosensors Cav-1 IGF-1R |
| title | Periodic Mechanical Stress Stimulates Cav-1-Dependent IGF-1R Mitogenic Signals in Rat Chondrocytes Through ERK1/2 |
| title_full | Periodic Mechanical Stress Stimulates Cav-1-Dependent IGF-1R Mitogenic Signals in Rat Chondrocytes Through ERK1/2 |
| title_fullStr | Periodic Mechanical Stress Stimulates Cav-1-Dependent IGF-1R Mitogenic Signals in Rat Chondrocytes Through ERK1/2 |
| title_full_unstemmed | Periodic Mechanical Stress Stimulates Cav-1-Dependent IGF-1R Mitogenic Signals in Rat Chondrocytes Through ERK1/2 |
| title_short | Periodic Mechanical Stress Stimulates Cav-1-Dependent IGF-1R Mitogenic Signals in Rat Chondrocytes Through ERK1/2 |
| title_sort | periodic mechanical stress stimulates cav 1 dependent igf 1r mitogenic signals in rat chondrocytes through erk1 2 |
| topic | Periodic mechanical stress Chondrocyte proliferation Non-integrin mechanosensors Cav-1 IGF-1R |
| url | https://www.karger.com/Article/FullText/492288 |
| work_keys_str_mv | AT keweiren periodicmechanicalstressstimulatescav1dependentigf1rmitogenicsignalsinratchondrocytesthrougherk12 AT jileitang periodicmechanicalstressstimulatescav1dependentigf1rmitogenicsignalsinratchondrocytesthrougherk12 AT xuefengjiang periodicmechanicalstressstimulatescav1dependentigf1rmitogenicsignalsinratchondrocytesthrougherk12 AT huiqingsun periodicmechanicalstressstimulatescav1dependentigf1rmitogenicsignalsinratchondrocytesthrougherk12 AT lumingnong periodicmechanicalstressstimulatescav1dependentigf1rmitogenicsignalsinratchondrocytesthrougherk12 AT nanshen periodicmechanicalstressstimulatescav1dependentigf1rmitogenicsignalsinratchondrocytesthrougherk12 AT yanqinggu periodicmechanicalstressstimulatescav1dependentigf1rmitogenicsignalsinratchondrocytesthrougherk12 |