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Article: PRIMUS: Comprehensive proteomics of mouse intervertebral discs that inform novel biology and relevance to human disease modelling

TitlePRIMUS: Comprehensive proteomics of mouse intervertebral discs that inform novel biology and relevance to human disease modelling
Authors
KeywordsMouse intervertebral disc
Label free quantitation
Proteomics
Extracellular matrix
Nucleus pulposus
Annulus fibrosus
Issue Date2021
PublisherElsevier BV. The Journal's web site is located at https://www.journals.elsevier.com/matrix-biology-plus
Citation
Matrix Biology Plus, 2021, v. 12, article no. 100082 How to Cite?
AbstractMice 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.
Persistent Identifierhttp://hdl.handle.net/10722/304883
ISSN
2023 SCImago Journal Rankings: 1.236
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorKudelko, M-
dc.contributor.authorChen, P-
dc.contributor.authorTam, V-
dc.contributor.authorZhang, Y-
dc.contributor.authorKong, OY-
dc.contributor.authorSharma, R-
dc.contributor.authorAu, TYK-
dc.contributor.authorTo, MKT-
dc.contributor.authorCheah, KSE-
dc.contributor.authorChan, WCW-
dc.contributor.authorChan, D-
dc.date.accessioned2021-10-05T02:36:35Z-
dc.date.available2021-10-05T02:36:35Z-
dc.date.issued2021-
dc.identifier.citationMatrix Biology Plus, 2021, v. 12, article no. 100082-
dc.identifier.issn2590-0285-
dc.identifier.urihttp://hdl.handle.net/10722/304883-
dc.description.abstractMice 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.-
dc.languageeng-
dc.publisherElsevier BV. The Journal's web site is located at https://www.journals.elsevier.com/matrix-biology-plus-
dc.relation.ispartofMatrix Biology Plus-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectMouse intervertebral disc-
dc.subjectLabel free quantitation-
dc.subjectProteomics-
dc.subjectExtracellular matrix-
dc.subjectNucleus pulposus-
dc.subjectAnnulus fibrosus-
dc.titlePRIMUS: Comprehensive proteomics of mouse intervertebral discs that inform novel biology and relevance to human disease modelling-
dc.typeArticle-
dc.identifier.emailTam, V: vivtam@hku.hk-
dc.identifier.emailZhang, Y: joycezy@hku.hk-
dc.identifier.emailSharma, R: rasharma@hku.hk-
dc.identifier.emailAu, TYK: tiffany_au@hku.hk-
dc.identifier.emailTo, MKT: mikektto@hku.hk-
dc.identifier.emailCheah, KSE: hrmbdkc@hku.hk-
dc.identifier.emailChan, WCW: cwilson@hku.hk-
dc.identifier.emailChan, D: chand@hku.hk-
dc.identifier.authorityTo, MKT=rp00302-
dc.identifier.authorityCheah, KSE=rp00342-
dc.identifier.authorityChan, D=rp00540-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.mbplus.2021.100082-
dc.identifier.pmid34409283-
dc.identifier.pmcidPMC8361275-
dc.identifier.scopuseid_2-s2.0-85112654292-
dc.identifier.hkuros326071-
dc.identifier.volume12-
dc.identifier.spagearticle no. 100082-
dc.identifier.epagearticle no. 100082-
dc.publisher.placeNetherlands-

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