PRIMUS: Comprehensive proteomics of mouse intervertebral discs that inform novel biology and relevance to human disease modelling
| Autor: | Peikai Chen, Daniel W. Chan, Michael Kai-Tsun To, Wilson C.W. Chan, Ying Zhang, Tiffany Y. K. Au, Mateusz Kudelko, Kathryn S.E. Cheah, Rakesh Sharma, Oi-Yin Kong, Vivian W.Y. Tam |
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| Rok vydání: | 2021 |
| Předmět: |
Label free quantitation
Proteomics musculoskeletal diseases Histology QH301-705.5 IAF inner AF Biophysics Nucleus pulposus Biology IDD intervertebral disc degeneration CDH2 Biochemistry Full Length Article Lipid droplet Genetics Biology (General) Molecular Biology Proteomic Profiling OAF outer AF Translation (biology) IVD intervertebral disc Extracellular matrix Cell Biology musculoskeletal system ECM extracellular matrix Cell biology NP nucleus pulposus Label-free quantification AF annulus fibrosus DEP differentially expressed protein Mouse intervertebral disc Proteome NLC notochordal-like cell Annulus fibrosus Function (biology) |
| Zdroj: | Matrix Biology Plus, Vol 12, Iss, Pp 100082-(2021) Matrix Biology Plus |
| ISSN: | 2590-0285 |
| DOI: | 10.1016/j.mbplus.2021.100082 |
| Popis: | Highlights • Proteomics of healthy mouse IVDs differentiating compartments and spine levels. • NP cells feature vacuoles with lysosomal, transport and cell–cell communication functions. • Collagen XII, decorin and other ECM proteins contribute to function of the AF. • Distinct proteomics between lumbar and tail discs. • Mouse is a relevant model for human disc biology but care is needed in its use. Mice are commonly used to study intervertebral disc (IVD) biology and related diseases such as IVD degeneration. Discs from both the lumbar and tail regions are used. However, little is known about compartmental characteristics in the different regions, nor their relevance to the human setting, where a functional IVD unit depends on a homeostatic proteome. Here, we address these major gaps through comprehensive proteomic profiling and in-depth analyses of 8-week-old healthy murine discs, followed by comparisons with human. Leveraging on a dataset of over 2,700 proteins from 31 proteomic profiles, we identified key molecular and cellular differences between disc compartments and spine levels, but not gender. The nucleus pulposus (NP) and annulus fibrosus (AF) compartments differ the most, both in matrisome and cellularity contents. Differences in the matrisome are consistent with the fibrous nature required for tensile strength in the AF and hydration property in the NP. Novel findings for the NP cells included an enrichment in cell junction proteins for cell–cell communication (Cdh2, Dsp and Gja1) and osmoregulation (Slc12a2 and Wnk1). In NP cells, we detected heterogeneity of vacuolar organelles; where about half have potential lysosomal function (Vamp3, Copb2, Lamp1/2, Lamtor1), some contain lipid droplets and others with undefined contents. The AF is enriched in proteins for the oxidative stress responses (Sod3 and Clu). Interestingly, mitochondrial proteins are elevated in the lumbar than tail IVDs that may reflect differences in metabolic requirement. Relative to the human, cellular and structural information are conserved for the AF. Even though the NP is more divergent between mouse and human, there are similarities at the level of cell biology. Further, common cross-species markers were identified for both NP (KRT8/19, CD109) and AF (COL12A1). Overall, mouse is a relevant model to study IVD biology, and an understanding of the limitation will facilitate research planning and data interpretation, maximizing the translation of research findings to human IVDs. |
| Databáze: | OpenAIRE |
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