Involvement of Autophagy in Rat Tail Static Compression-Induced Intervertebral Disc Degeneration and Notochordal Cell Disappearance
The intervertebral disc is the largest avascular low-nutrient organ in the body. Thus, resident cells may utilize autophagy, a stress-response survival mechanism, by self-digesting and recycling damaged components. Our objective was to elucidate the involvement of autophagy in rat experimental disc...
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MDPI AG
2021-05-01
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| Series: | International Journal of Molecular Sciences |
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| author | Takashi Yurube Hiroaki Hirata Masaaki Ito Yoshiki Terashima Yuji Kakiuchi Ryosuke Kuroda Kenichiro Kakutani |
| author_facet | Takashi Yurube Hiroaki Hirata Masaaki Ito Yoshiki Terashima Yuji Kakiuchi Ryosuke Kuroda Kenichiro Kakutani |
| author_sort | Takashi Yurube |
| collection | DOAJ |
| description | The intervertebral disc is the largest avascular low-nutrient organ in the body. Thus, resident cells may utilize autophagy, a stress-response survival mechanism, by self-digesting and recycling damaged components. Our objective was to elucidate the involvement of autophagy in rat experimental disc degeneration. In vitro, the comparison between human and rat disc nucleus pulposus (NP) and annulus fibrosus (AF) cells found increased autophagic flux under serum deprivation rather in humans than in rats and in NP cells than in AF cells of rats (<i>n</i> = 6). In vivo, time-course Western blotting showed more distinct basal autophagy in rat tail disc NP tissues than in AF tissues; however, both decreased under sustained static compression (<i>n</i> = 24). Then, immunohistochemistry displayed abundant autophagy-related protein expression in large vacuolated disc NP notochordal cells of sham rats. Under temporary static compression (<i>n</i> = 18), multi-color immunofluorescence further identified rapidly decreased brachyury-positive notochordal cells with robust expression of autophagic microtubule-associated protein 1 light chain 3 (LC3) and transiently increased brachyury-negative non-notochordal cells with weaker LC3 expression. Notably, terminal deoxynucleotidyl transferase dUTP nick end labeling-positive apoptotic death was predominant in brachyury-negative non-notochordal cells. Based on the observed notochordal cell autophagy impairment and non-notochordal cell apoptosis induction under unphysiological mechanical loading, further investigation is warranted to clarify possible autophagy-induced protection against notochordal cell disappearance, the earliest sign of disc degeneration, through limiting apoptosis. |
| first_indexed | 2024-03-10T11:02:08Z |
| format | Article |
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| language | English |
| last_indexed | 2024-03-10T11:02:08Z |
| publishDate | 2021-05-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1601909ab62f41b580cb9ac50a723d202023-11-21T21:26:11ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-012211564810.3390/ijms22115648Involvement of Autophagy in Rat Tail Static Compression-Induced Intervertebral Disc Degeneration and Notochordal Cell DisappearanceTakashi Yurube0Hiroaki Hirata1Masaaki Ito2Yoshiki Terashima3Yuji Kakiuchi4Ryosuke Kuroda5Kenichiro Kakutani6Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, JapanDepartment of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, JapanDepartment of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, JapanDepartment of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, JapanDepartment of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, JapanDepartment of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, JapanDepartment of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, JapanThe intervertebral disc is the largest avascular low-nutrient organ in the body. Thus, resident cells may utilize autophagy, a stress-response survival mechanism, by self-digesting and recycling damaged components. Our objective was to elucidate the involvement of autophagy in rat experimental disc degeneration. In vitro, the comparison between human and rat disc nucleus pulposus (NP) and annulus fibrosus (AF) cells found increased autophagic flux under serum deprivation rather in humans than in rats and in NP cells than in AF cells of rats (<i>n</i> = 6). In vivo, time-course Western blotting showed more distinct basal autophagy in rat tail disc NP tissues than in AF tissues; however, both decreased under sustained static compression (<i>n</i> = 24). Then, immunohistochemistry displayed abundant autophagy-related protein expression in large vacuolated disc NP notochordal cells of sham rats. Under temporary static compression (<i>n</i> = 18), multi-color immunofluorescence further identified rapidly decreased brachyury-positive notochordal cells with robust expression of autophagic microtubule-associated protein 1 light chain 3 (LC3) and transiently increased brachyury-negative non-notochordal cells with weaker LC3 expression. Notably, terminal deoxynucleotidyl transferase dUTP nick end labeling-positive apoptotic death was predominant in brachyury-negative non-notochordal cells. Based on the observed notochordal cell autophagy impairment and non-notochordal cell apoptosis induction under unphysiological mechanical loading, further investigation is warranted to clarify possible autophagy-induced protection against notochordal cell disappearance, the earliest sign of disc degeneration, through limiting apoptosis.https://www.mdpi.com/1422-0067/22/11/5648intervertebral disc degenerationnucleus pulposusnotochordal cellsautophagyapoptosisnutrient deprivation |
| spellingShingle | Takashi Yurube Hiroaki Hirata Masaaki Ito Yoshiki Terashima Yuji Kakiuchi Ryosuke Kuroda Kenichiro Kakutani Involvement of Autophagy in Rat Tail Static Compression-Induced Intervertebral Disc Degeneration and Notochordal Cell Disappearance International Journal of Molecular Sciences intervertebral disc degeneration nucleus pulposus notochordal cells autophagy apoptosis nutrient deprivation |
| title | Involvement of Autophagy in Rat Tail Static Compression-Induced Intervertebral Disc Degeneration and Notochordal Cell Disappearance |
| title_full | Involvement of Autophagy in Rat Tail Static Compression-Induced Intervertebral Disc Degeneration and Notochordal Cell Disappearance |
| title_fullStr | Involvement of Autophagy in Rat Tail Static Compression-Induced Intervertebral Disc Degeneration and Notochordal Cell Disappearance |
| title_full_unstemmed | Involvement of Autophagy in Rat Tail Static Compression-Induced Intervertebral Disc Degeneration and Notochordal Cell Disappearance |
| title_short | Involvement of Autophagy in Rat Tail Static Compression-Induced Intervertebral Disc Degeneration and Notochordal Cell Disappearance |
| title_sort | involvement of autophagy in rat tail static compression induced intervertebral disc degeneration and notochordal cell disappearance |
| topic | intervertebral disc degeneration nucleus pulposus notochordal cells autophagy apoptosis nutrient deprivation |
| url | https://www.mdpi.com/1422-0067/22/11/5648 |
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