The Immune Privilege of the Intervertebral Disc: Implications for Intervertebral Disc Degeneration Treatment

Sun, Zhen; Liu, Bing; Luo, Zhuojing

doi:10.7150/ijms.42238

Cited by 131 publications

(156 citation statements)

References 87 publications

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“…Interestingly, these modules all showed a tendency for convex patterns with upward expression toward the OAF regions, in both lateral and anteroposterior directions, in all levels, combined or separated (Figure 3F-H; Figure 3-figure supplement 3B-D). The higher proportions of ECM, muscle contraction and immune system proteins in the OAF are consistent with the contractile function of the AF (Nakai et al, 2016), and with the NP being avascular and "immune-privileged" in a young homeostatic environment (Sun et al, 2020).…”

Section: Expression Modules Show Lateral and Anteroposterior Trendssupporting

confidence: 62%

DIPPER, a spatiotemporal proteomics atlas of human intervertebral discs for exploring ageing and degeneration dynamics

Tam

Chen

Yee

et al. 2020

eLife

114

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The spatiotemporal proteome of the intervertebral disc (IVD) underpins its integrity and function. We present DIPPER, a deep and comprehensive IVD proteomic resource comprising 94 genome-wide profiles from 17 individuals. To begin with, protein modules defining key directional trends spanning the lateral and anteroposterior axes were derived from high-resolution spatial proteomes of intact young cadaveric lumbar IVDs. They revealed novel region-specific profiles of regulatory activities and displayed potential paths of deconstruction in the level- and location-matched aged cadaveric discs. Machine learning methods predicted a ‘hydration matrisome’ that connects extracellular matrix with MRI intensity. Importantly, the static proteome used as point-references can be integrated with dynamic proteome (SILAC/degradome) and transcriptome data from multiple clinical samples, enhancing robustness and clinical relevance. The data, findings, and methodology, available on a web interface (http://www.sbms.hku.hk/dclab/DIPPER/), will be valuable references in the field of IVD biology and proteomic analytics.

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Section: Expression Modules Show Lateral and Anteroposterior Trendssupporting

confidence: 62%

DIPPER, a spatiotemporal proteomics atlas of human intervertebral discs for exploring ageing and degeneration dynamics

Tam

Chen

Yee

et al. 2020

eLife

114

View full text Add to dashboard Cite

show abstract

“…Interestingly, these modules all showed a tendency for convex patterns with upward expression toward the OAF regions, in both lateral and anteroposterior directions, in all levels, combined or separated ( Figure 3F-H; Supplemental S8B-D). The higher proportions of ECM, muscle contraction and immune system proteins in the OAF are consistent with the contractile function of the AF (Nakai et al, 2016), and with the NP being avascular and "immune-privileged" in a young homeostatic environment (Sun et al, 2020).…”

Section: Expression Modules Show Lateral and Anteroposterior Trendssupporting

confidence: 62%

DIPPER: a spatiotemporal proteomics atlas of human intervertebral discs for exploring ageing and degeneration dynamics

Tam

Chen

Yee

et al. 2020

Preprint

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The proteome of the human intervertebral disc, particularly the extracellular matrix, underpins its integrity and function. We describe high quality spatial proteomes from young and aged lumbar discs, profiled across different regions, and identified sets of proteins that are variable or constant with respect to disc compartments, levels, and anatomic directions. From these, four protein modules defining a young disc were derived. Mapping these modules to aged disc proteomes showed that the central nucleus pulposus becomes more like the outer annulus fibrosus. Transcriptome analysis supported these proteomic findings. Concurrently, dynamic proteomic analyses indicate impaired protein synthesis and increased degradative activities. We identified a novel set of proteins that correlates with disc hydration that are predictive of MRI intensities. Signalling pathways (SHH, WNT, BMP/TGFβ) and hypertrophic chondrocyte differentiation events relating to ageing and degeneration were implicated. This work presents the foundation proteomic architectural landscapes of young and ageing human discs.

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“…However, the disappearance of notochordal cells in human IVD is a matter of debate, since a considerable proportion of cells within NP of adults display notochord-like phenotype [ 15 ]. Animal studies found that both NP cells and notochordal cells originate from the embryonic notochord [ 14 ].…”

Section: On Intervertebral Discmentioning

confidence: 99%

Intervertebral Disc and Adipokine Leptin—Loves Me, Loves Me Not

Ćurić

2020

IJMS

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Leptin—the most famous adipose tissue-secreted hormone—in the human body is mostly observed in a negative connotation, as the hormone level increases with the accumulation of body fat. Nowadays, fatness is becoming another normal body shape. Fatness is burdened with numerous illnesses—including low back pain and degenerative disease of lumbar intervertebral disc (IVD). IVD degeneration and IVD inflammation are two indiscerptible phenomena. Irrespective of the underlying pathophysiological background (trauma, obesity, nutrient deficiency), the inflammation is crucial in triggering IVD degeneration. Leptin is usually depicted as a proinflammatory adipokine. Many studies aimed at explaining the role of leptin in IVD degeneration, though mostly in in vitro and on animal models, confirmed leptin’s “bad reputation”. However, several studies found that leptin might have protective role in IVD metabolism. This review examines the current literature on the metabolic role of different depots of adipose tissue, with focus on leptin, in pathogenesis of IVD degeneration.

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The Immune Privilege of the Intervertebral Disc: Implications for Intervertebral Disc Degeneration Treatment

Cited by 131 publications

References 87 publications

DIPPER, a spatiotemporal proteomics atlas of human intervertebral discs for exploring ageing and degeneration dynamics

DIPPER, a spatiotemporal proteomics atlas of human intervertebral discs for exploring ageing and degeneration dynamics

DIPPER: a spatiotemporal proteomics atlas of human intervertebral discs for exploring ageing and degeneration dynamics

Intervertebral Disc and Adipokine Leptin—Loves Me, Loves Me Not

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