PMID- 37090223
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230425
IS  - 2666-5484 (Electronic)
IS  - 2666-5484 (Linking)
VI  - 14
DP  - 2023 Jun
TI  - Intervertebral disc cell fate during aging and degeneration: apoptosis, 
      senescence, and autophagy.
PG  - 100210
LID - 10.1016/j.xnsj.2023.100210 [doi]
LID - 100210
AB  - 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.
CI  - (c) 2023 The Author(s).
FAU - Yurube, Takashi
AU  - Yurube T
AD  - Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 
      7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
FAU - Takeoka, Yoshiki
AU  - Takeoka Y
AD  - Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 
      7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
FAU - Kanda, Yutaro
AU  - Kanda Y
AD  - Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 
      7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
FAU - Kuroda, Ryosuke
AU  - Kuroda R
AD  - Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 
      7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
FAU - Kakutani, Kenichiro
AU  - Kakutani K
AD  - Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 
      7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
LA  - eng
PT  - Journal Article
DEP - 20230311
PL  - United States
TA  - N Am Spine Soc J
JT  - North American Spine Society journal
JID - 9918335076906676
PMC - PMC10113901
OTO - NOTNLM
OT  - Aging
OT  - Apoptosis
OT  - Autophagy
OT  - Degeneration
OT  - Intervertebral disc
OT  - Mammalian target of rapamycin (mTOR)
OT  - Phenotype
OT  - Senescence
OT  - Spine
COIS- The authors declare that they have no known competing financial interests or 
      personal relationships that could have appeared to influence the work reported in 
      this paper.
EDAT- 2023/04/24 06:42
MHDA- 2023/04/24 06:43
PMCR- 2023/03/11
CRDT- 2023/04/24 03:39
PHST- 2023/01/03 00:00 [received]
PHST- 2023/02/25 00:00 [revised]
PHST- 2023/03/06 00:00 [accepted]
PHST- 2023/04/24 06:43 [medline]
PHST- 2023/04/24 06:42 [pubmed]
PHST- 2023/04/24 03:39 [entrez]
PHST- 2023/03/11 00:00 [pmc-release]
AID - S2666-5484(23)00012-4 [pii]
AID - 100210 [pii]
AID - 10.1016/j.xnsj.2023.100210 [doi]
PST - epublish
SO  - N Am Spine Soc J. 2023 Mar 11;14:100210. doi: 10.1016/j.xnsj.2023.100210. 
      eCollection 2023 Jun.