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Proteinases involved in matrix turnover during cartilage and bone breakdown

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Abstract

The joint is a discrete unit that consists of cartilage, bone, tendon and ligaments. These tissues are all composed of an extracellular matrix made of collagens, proteoglycans and specialised glycoproteins that are actively synthesised, precisely assembled and subsequently degraded by the resident connective tissue cells. A balance is maintained between matrix synthesis and degradation in healthy adult tissues. Different classes of proteinases play a part in connective tissue turnover in which active proteinases can cleave matrix protein during resorption, although the proteinase that predominates varies between different tissues and diseases. The metalloproteinases are potent enzymes that, once activated, degrade connective tissue and are inhibited by tissue inhibitors of metalloproteinases (TIMPs); the balance between active matrix metalloproteinases and TIMPs determines, in many tissues, the extent of extracellular matrix degradation. The serine proteinases are involved in the initiation of activation cascades and some, such as elastase, can directly degrade the matrix. Cysteine proteinases are responsible for the breakdown of collagen in bone following the removal of the osteoid layer and the attachment of osteoclasts to the exposed bone surface. Various growth factors increase the synthesis of matrix and proteinase inhibitors, whereas cytokines (alone or in combination) can inhibit matrix synthesis and stimulate proteinase production and matrix destruction.

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Abbreviations

ADAM:

a disintegrin and metalloproteinase

ADAMTS:

a disintegrin and metalloproteinase with thrombospondin motifs

BMP-1:

bone morphogenetic protein-1

ECM:

extracellular matrix

GPI:

glycosylphosphatidyl inositol

HDAC:

histone deacetylase

IGFBP:

insulin-like growth factor binding protein

IL:

interleukin

Jak-STAT:

Janus kinase-signal transducer and activator of transcription

MAPK:

mitogen-activated protein kinase

MMPs:

matrix metalloproteinases

NF-κB:

nuclear factor kappa B

OA:

osteoarthritis

OSM:

oncostatin M

RA:

rheumatoid arthritis

RANKL:

receptor activator of nuclear factor κB ligand

TNF:

tumour necrosis factor

TIMPs:

tissue inhibitors of metalloproteinases

TGF:

transforming growth factor

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Acknowledgements

We thank the UK NIHR Biomedical Research Centre for Ageing and Age-related disease award to the Newcastle upon Tyne Hospitals NHS Foundation Trust, Arthritis Research Campaign, the Wellcome Trust, FARNE, Dunhill Medical Trust, JGW Patterson Foundation and the Nuffield Foundation (Oliver Bird Fund) for financial support.

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  1. Musculoskeletal Research Group, Institute of Cellular Medicine, The Medical School, University of Newcastle upon Tyne, 4th Floor Cookson Building, Newcastle upon Tyne, NE2 4HH, UK

    Tim E. Cawston & David A. Young

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Correspondence to Tim E. Cawston.

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Cawston, T.E., Young, D.A. Proteinases involved in matrix turnover during cartilage and bone breakdown. Cell Tissue Res 339, 221–235 (2010). https://doi.org/10.1007/s00441-009-0887-6

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