Intervertebral disc cell fate during aging and degeneration: apoptosis, senescence, and autophagy
ABSTRACT: Background: Degenerative disc disease, a major cause of low back pain and associated neurological symptoms, is a global health problem with the high morbidity, workforce loss, and socioeconomic burden. The present surgical strategy of disc resection and/or spinal fusion results in the fun...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | North American Spine Society Journal |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666548423000124 |
| _version_ | 1797796353977352192 |
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| author | Takashi Yurube, M.D., Ph.D. Yoshiki Takeoka, M.D., Ph.D. Yutaro Kanda, M.D., Ph.D. Ryosuke Kuroda, M.D., Ph.D. Kenichiro Kakutani, M.D., Ph.D. |
| author_facet | Takashi Yurube, M.D., Ph.D. Yoshiki Takeoka, M.D., Ph.D. Yutaro Kanda, M.D., Ph.D. Ryosuke Kuroda, M.D., Ph.D. Kenichiro Kakutani, M.D., Ph.D. |
| author_sort | Takashi Yurube, M.D., Ph.D. |
| collection | DOAJ |
| description | ABSTRACT: Background: Degenerative disc disease, a major cause of low back pain and associated neurological symptoms, is a global health problem with the high morbidity, workforce loss, and socioeconomic burden. The present surgical strategy of disc resection and/or spinal fusion results in the functional loss of load, shock absorption, and movement; therefore, the development of new biological therapies is demanded. This achievement requires the understanding of intervertebral disc cell fate during aging and degeneration. Methods: Literature review was performed to clarify the current concepts and future perspectives of disc cell fate, focused on apoptosis, senescence, and autophagy. Results: The intervertebral disc has a complex structure with the nucleus pulposus (NP), annulus fibrosus (AF), and cartilage endplates. While the AF arises from the mesenchyme, the NP originates from the notochord. Human disc NP notochordal phenotype disappears in adolescence, accompanied with cell death induction and chondrocyte proliferation. Discs morphologically and biochemically degenerate from early childhood as well, thereby suggesting a possible involvement of cell fate including age-related phenotypic changes in the disease process. As the disc is the largest avascular organ in the body, nutrient deprivation is a suspected contributor to degeneration. During aging and degeneration, disc cells undergo senescence, irreversible growth arrest, producing proinflammatory cytokines and matrix-degradative enzymes. Excessive stress ultimately leads to programmed cell death including apoptosis, necroptosis, pyroptosis, and ferroptosis. Autophagy, the intracellular degradation and recycling system, plays a role in maintaining cell homeostasis. While the incidence of apoptosis and senescence increases with age and degeneration severity, autophagy can be activated earlier, in response to limited nutrition and inflammation, but impaired in aged, degenerated discs. The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) is a signal integrator to determine disc cell fate. Conclusions: Cell fate and microenvironmental regulation by modulating PI3K/Akt/mTOR signaling is a potential biological treatment for degenerative disc disease. |
| first_indexed | 2024-03-13T03:31:49Z |
| format | Article |
| id | doaj.art-db9c5aa097ec4718906d9730029062fd |
| institution | Directory Open Access Journal |
| issn | 2666-5484 |
| language | English |
| last_indexed | 2024-03-13T03:31:49Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | North American Spine Society Journal |
| spelling | doaj.art-db9c5aa097ec4718906d9730029062fd2023-06-24T05:19:18ZengElsevierNorth American Spine Society Journal2666-54842023-06-0114100210Intervertebral disc cell fate during aging and degeneration: apoptosis, senescence, and autophagyTakashi Yurube, M.D., Ph.D.0Yoshiki Takeoka, M.D., Ph.D.1Yutaro Kanda, M.D., Ph.D.2Ryosuke Kuroda, M.D., Ph.D.3Kenichiro Kakutani, M.D., Ph.D.4Corresponding author. Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. Tel.: +(81) 78-3825985; Fax: +(81) 78-3516944.; Department 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, JapanABSTRACT: Background: Degenerative disc disease, a major cause of low back pain and associated neurological symptoms, is a global health problem with the high morbidity, workforce loss, and socioeconomic burden. The present surgical strategy of disc resection and/or spinal fusion results in the functional loss of load, shock absorption, and movement; therefore, the development of new biological therapies is demanded. This achievement requires the understanding of intervertebral disc cell fate during aging and degeneration. Methods: Literature review was performed to clarify the current concepts and future perspectives of disc cell fate, focused on apoptosis, senescence, and autophagy. Results: The intervertebral disc has a complex structure with the nucleus pulposus (NP), annulus fibrosus (AF), and cartilage endplates. While the AF arises from the mesenchyme, the NP originates from the notochord. Human disc NP notochordal phenotype disappears in adolescence, accompanied with cell death induction and chondrocyte proliferation. Discs morphologically and biochemically degenerate from early childhood as well, thereby suggesting a possible involvement of cell fate including age-related phenotypic changes in the disease process. As the disc is the largest avascular organ in the body, nutrient deprivation is a suspected contributor to degeneration. During aging and degeneration, disc cells undergo senescence, irreversible growth arrest, producing proinflammatory cytokines and matrix-degradative enzymes. Excessive stress ultimately leads to programmed cell death including apoptosis, necroptosis, pyroptosis, and ferroptosis. Autophagy, the intracellular degradation and recycling system, plays a role in maintaining cell homeostasis. While the incidence of apoptosis and senescence increases with age and degeneration severity, autophagy can be activated earlier, in response to limited nutrition and inflammation, but impaired in aged, degenerated discs. The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) is a signal integrator to determine disc cell fate. Conclusions: Cell fate and microenvironmental regulation by modulating PI3K/Akt/mTOR signaling is a potential biological treatment for degenerative disc disease.http://www.sciencedirect.com/science/article/pii/S2666548423000124Intervertebral discAgingDegenerationPhenotypeApoptosisSenescence |
| spellingShingle | Takashi Yurube, M.D., Ph.D. Yoshiki Takeoka, M.D., Ph.D. Yutaro Kanda, M.D., Ph.D. Ryosuke Kuroda, M.D., Ph.D. Kenichiro Kakutani, M.D., Ph.D. Intervertebral disc cell fate during aging and degeneration: apoptosis, senescence, and autophagy North American Spine Society Journal Intervertebral disc Aging Degeneration Phenotype Apoptosis Senescence |
| title | Intervertebral disc cell fate during aging and degeneration: apoptosis, senescence, and autophagy |
| title_full | Intervertebral disc cell fate during aging and degeneration: apoptosis, senescence, and autophagy |
| title_fullStr | Intervertebral disc cell fate during aging and degeneration: apoptosis, senescence, and autophagy |
| title_full_unstemmed | Intervertebral disc cell fate during aging and degeneration: apoptosis, senescence, and autophagy |
| title_short | Intervertebral disc cell fate during aging and degeneration: apoptosis, senescence, and autophagy |
| title_sort | intervertebral disc cell fate during aging and degeneration apoptosis senescence and autophagy |
| topic | Intervertebral disc Aging Degeneration Phenotype Apoptosis Senescence |
| url | http://www.sciencedirect.com/science/article/pii/S2666548423000124 |
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