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Type XI collagen–perlecan–HS interactions stabilise the pericellular matrix of annulus fibrosus cells and chondrocytes providing matrix stabilisation and homeostasis

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Abstract

The aim of this study was to ascertain whether, like many cell types in cartilaginous tissues if type XI collagen was a pericellular component of annulus fibrosus (AF) cells and chondrocytes. Fine fibrillar networks were visualised which were perlecan, HS (MAb 10E4) and type XI collagen positive. Heparitinase-III pre-digestion abolished the type XI collagen and 10E4 localisation in these fibrillar assemblies demonstrating a putative HS mediated interaction which localised the type XI collagen. Type XI collagen was confirmed to be present in the Heparitinase III treated AF monolayer media samples by immunoblotting. Heparitinase-III generated ΔHS stub epitopes throughout these fibrillar networks strongly visualised by MAb 3-G-10. Monolayers of murine hip articular chondrocytes from C57BL/6 and Hspg2 exon 3 null mice also displayed pericellular perlecan localisations, however type XI collagen was only evident in the Wild type mice. Perlecan was also immunolocalised in control and murine knee articular cartilage from the two mouse genotypes subjected to a medial meniscal destabilisation procedure which induces OA. This resulted in a severe depletion of perlecan levels particularly in the perlecan exon 3 null mice and was consistent with OA representing a disease of the pericellular matrix. A model was prepared to explain these observations between the NPP type XI collagen domain and HS chains of perlecan domain-I in the pericellular matrix of AF cells which likely contributed to cellular communication, tissue stabilization and the regulation of extracellular matrix homeostasis.

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Abbreviations

IVD:

Intervertebral disc

AF:

Annulus fibrosus

HS:

Heparan sulfate

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Acknowledgements

This study was funded by NHMRC Project Grant 352562. Prof David Eyre and Dr James Wu are thanked for the kind gift of a type XI collagen stanard and Dr C Shu for provision of murine cartilage specimens from C57BL/6 and perlecan exon 3 null mice.

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Authors and Affiliations

  1. Raymond Purves Bone and Joint Research Laboratories, Level 10, Kolling Institute of Medical Research B6, The Royal North Shore Hospital, St. Leonards, NSW, 2065, Australia

    Susan M. Smith & James Melrose

  2. Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW, 2052, Australia

    James Melrose

  3. Sydney Medical School, Northern, The University of Sydney, St. Leonards, 2065, NSW, Australia

    James Melrose

  4. Faculty of Medicine and Health, Royal North Shore Hospital, University of Sydney, St. Leonards, NSW, 2065, Australia

    James Melrose

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Smith, S.M., Melrose, J. Type XI collagen–perlecan–HS interactions stabilise the pericellular matrix of annulus fibrosus cells and chondrocytes providing matrix stabilisation and homeostasis. J Mol Hist 50, 285–294 (2019). https://doi.org/10.1007/s10735-019-09823-1

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