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Cells
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Novel Insights into Mechanism and Treatment of Degenerative Disc Disease
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Novel Insights into Mechanism and Treatment of Degenerative Disc Disease

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: 30 June 2026 | Viewed by 7015

Special Issue Editor

Dr. Yejia Zhang

E-Mail Website
Guest Editor
Physical Medicine and Rehabilitation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Interests: cell and molecular biology; spine; intervertebral disc

Special Issue Information

Dear Colleagues,

Back pain related to the degeneration of IVDs is a prevalent clinical problem, but the study of intervertebral disc (IVD) degeneration has advanced in recent years. For example, we have utilized innovative molecular and tissue engineering techniques to understand how age, genetics, and injury affect IVD degeneration, and have tested novel treatments in animal models and organ/cell culture systems.

We encourage authors to submit their work in the form of original research or review articles that discuss the disease mechanism and innovative treatment strategies. This Special Issue also welcomes the submission of articles based on human patients, animal models or organ/cell culture studies. The scope of this Special Issue also includes novel technologies that enable the exploration of important disease characteristics and mechanisms, new discoveries, and the development of innovative therapies.

Dr. Yejia Zhang
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • intervertebral disc (IVD) degeneration
  • back pain
  • age
  • genetics
  • injury

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Published Papers (4 papers)

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Research

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11 pages, 1733 KB  
Article
Effects of Age on Intervertebral Disc Tissue Morphology and Gene Expression in the ADAM8-Inactivation Mouse
by Lutian Yao, Huan Wang, Zuozhen Tian, Frances S. Shofer, Ling Qin and Yejia Zhang
Cells 2026, 15(8), 730; https://doi.org/10.3390/cells15080730 - 20 Apr 2026
Viewed by 428
Abstract
Purpose: To determine which age of mice should be used to compare the effects of ADAM8 mutation on intervertebral disc (IVD) responses to injury. Methods: IVDs of ADAM8 mutant (Adam8EQ) and wild type (WT) mice, aged 3, 10 [...] Read more.
Purpose: To determine which age of mice should be used to compare the effects of ADAM8 mutation on intervertebral disc (IVD) responses to injury. Methods: IVDs of ADAM8 mutant (Adam8EQ) and wild type (WT) mice, aged 3, 10 and 18 months were injured. IVD tissues were harvested 1 week post injury for histological and molecular studies. Results: Histological scores increased with aging in intact IVDs, and there were no differences between Adam8EQ and WT mice (n = 11–28; p > 0.05). Safranin O-staining was less intense in 10-month than in 3-month-old mice, in both intact and injured IVDs (n = 3–15; p < 0.05). Cxcl1, Il6, and Adam8 gene expression levels were higher in the injured tail IVDs of 3-month-old Adam8EQ than WT mice (n = 18–30; p < 0.05); the injury-related differences diminished with increasing age. Conclusions: No histological differences were found between Adam8EQ and WT mouse IVDs at 3, 10 or 18 months of age, in the intact or injured discs. The differences in inflammatory marker gene expression were detectable at age 3 months, but were less evident when the injury occurred at age 10 or 18 months. Therefore, to identify differences in injury responses between WT and Adam8EQ mouse IVDs, 3-month-old mice are superior to older mice. Full article
(This article belongs to the Special Issue Novel Insights into Mechanism and Treatment of Degenerative Disc Disease)
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22 pages, 4698 KB  
Article
Neuroimmune Activation in a Goat Model of Intervertebral Disc Degeneration
by Janai A. Augustin, Kevin G. Burt, Caitlin Barrett, Matthew Fainor, Brianna S. Orozco, Thomas P. Schaer, Harvey E. Smith, Robert L. Mauck and Sarah E. Gullbrand
Cells 2026, 15(3), 286; https://doi.org/10.3390/cells15030286 - 3 Feb 2026
Viewed by 1210
Abstract
Intervertebral disc degeneration (IVDD) initiates a cascade of structural and biological changes that compromise mechanical function, often leading to chronic pain. While small animal models have provided insight into inflammatory and nociceptive mechanisms of IVDD, translational studies require large animal models that more [...] Read more.
Intervertebral disc degeneration (IVDD) initiates a cascade of structural and biological changes that compromise mechanical function, often leading to chronic pain. While small animal models have provided insight into inflammatory and nociceptive mechanisms of IVDD, translational studies require large animal models that more closely replicate human spine anatomy and physiology. This study induced cervical disc degeneration via intradiscal chondroitinase ABC (ChABC) injection in a large animal model and evaluated the associated disc pathology and neuroinflammatory responses across IVDs and within spinal cord and dorsal root ganglia (DRG) tissues. Results confirmed structural degeneration at ChABC-injected levels and revealed additional evidence of adjacent segment degeneration. Neuroinflammatory analyses revealed innervation, via deposition of PGP9.5 and NFH, throughout both ChABC-injected and adjacent IVDs. Monocyte markers were significantly increased in ChABC-degenerated IVDs. Across experimental groups, the level of monocyte (Ly6C) and macrophage (CD68) markers correlated with worsened histological scores and with reduced mechanical integrity. Similarly, increased production of the neuropeptide, Substance P, in IVDs was significantly positively correlated with compromised IVD mechanical function. Finally, we observed elevated production of the microglia marker, Iba1, and Substance P production in the spinal cord, with similar trends in DRGs, in degenerative spines. By establishing quantitative relationships between disc pathology, immune responses, and neural activation, this work established possible disease-contributing neuroinflammatory activation and further validated a clinically relevant model for preclinical evaluation of regenerative and therapeutic strategies. Full article
(This article belongs to the Special Issue Novel Insights into Mechanism and Treatment of Degenerative Disc Disease)
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20 pages, 10292 KB  
Article
An Ex Vivo Intervertebral Disc Slice Culture Model for Studying Disc Degeneration and Immune Cell Interactions
by Eunha G. Oh, Li Xiao, Zhiwen Xu, Yuan Xing, Yi Zhang, Parastoo Anbaei, Jialun A. Chi, Li Jin, Rebecca R. Pompano and Xudong Li
Cells 2025, 14(16), 1230; https://doi.org/10.3390/cells14161230 - 8 Aug 2025
Cited by 2 | Viewed by 2098
Abstract
Intervertebral disc degeneration is a leading cause of back and leg pain and a major contributor to disability worldwide. Despite its prevalence, treatments remain limited due to incomplete understanding of its pathology. In vivo models pose challenges for controlled conditions, while in vitro [...] Read more.
Intervertebral disc degeneration is a leading cause of back and leg pain and a major contributor to disability worldwide. Despite its prevalence, treatments remain limited due to incomplete understanding of its pathology. In vivo models pose challenges for controlled conditions, while in vitro cell cultures lack key cell–cell and cell–matrix interactions. To address these limitations, we developed a novel tissue slice culture model of mouse discs, in which intact mouse discs were sliced down to 300 μm thickness with a vibratome and cultured ex vivo at various time points. The cell viability, matrix components, structure integrity, inflammatory responses, and macrophage interactions were evaluated with biochemistry, gene expression, histology, and 3D imaging analyses. Disc slices maintained structural integrity and cell viability, with preserved extracellular matrix in the annulus fibrosus (AF) and mild degeneration in nucleus pulposus (NP) by day 5. Interleukin-1 (IL-1) induced disc degeneration manifested by increased glycosaminoglycan release in media and reduced aggrecan and collagen II mRNA levels in disc cells. Cultured disc slices promoted macrophages towards pro-inflammatory phenotype with elevated mRNA levels of il-1α, il-6, and inos. Macrophage overlay and 3D imaging demonstrated macrophage infiltration into the NP and AF tissues up to ~100 µm in depth. The disc tissue slice model captures key features of intervertebral discs and can be used for investigating mechanisms of disc degeneration and therapeutic evaluation. Full article
(This article belongs to the Special Issue Novel Insights into Mechanism and Treatment of Degenerative Disc Disease)
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Review

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19 pages, 963 KB  
Review
Impact of Menopause and Associated Hormonal Changes on Spine Health in Older Females: A Review
by Julia Chagas, Gabrielle Gilmer, Gwendolyn Sowa and Nam Vo
Cells 2026, 15(2), 148; https://doi.org/10.3390/cells15020148 - 14 Jan 2026
Viewed by 2673
Abstract
Low back pain (LBP) represents a major societal and economic burden, with annual costs in the United States estimated at $90–134.5 billion. LBP disproportionately impacts postmenopausal women relative to age-matched men, suggesting a role for sex-specific biological factors. Although the mechanisms underlying this [...] Read more.
Low back pain (LBP) represents a major societal and economic burden, with annual costs in the United States estimated at $90–134.5 billion. LBP disproportionately impacts postmenopausal women relative to age-matched men, suggesting a role for sex-specific biological factors. Although the mechanisms underlying this disparity are not fully understood, hormonal imbalance during menopause may contribute to LBP pathophysiology. This narrative review aimed to elucidate the impact of menopause on LBP, with emphasis on hormonal effects on spinal tissues and systemic processes. A literature search was conducted, followed by screening of titles, abstracts, and full texts of original clinical studies, preclinical research using human or animal samples, and relevant reviews. Rigour and reproducibility were evaluated using the ARRIVE Guidelines and the Modified Downs & Black Checklist. Evidence indicates that menopause is associated with changes in intervertebral discs, facet joint, ligamentum flavum, skeletal muscle, sympathetic innervation, and systemic systems such as the gut microbiome. However, most findings are correlational rather than causal. Evidence supporting hormone replacement therapy for LBP remains inconclusive, whereas exercise and other treatments, including parathyroid hormones, show more consistent benefits. Future studies should focus on causal mechanisms and adhere to rigour guidelines to improve translational potential. Full article
(This article belongs to the Special Issue Novel Insights into Mechanism and Treatment of Degenerative Disc Disease)
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