Inflammation Research

, Volume 67, Issue 3, pp 219–231 | Cite as

Intracellular apoptotic pathways: a potential target for reducing joint damage in rheumatoid arthritis

Review

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that results in both local and systemic bone erosion, causing significant joint deformities and functional disability. The increased number of synovial fibroblasts, inflammatory cells and osteoclasts in RA is associated with reduced apoptosis in these cells. The ability to modulate the cell proliferation or death (particularly apoptosis) is recognised for its immense therapeutic potential. Identifying new therapeutics to assist in stimulating apoptosis within the synovial joints therefore may be beneficial in reducing inflammation and bone loss in RA patients. In this review, the roles of anti-apoptotic proteins that are upregulated in RA synovial joints will be discussed in relation to their actions on bone destruction and inflammation. Evidence recently published suggests that intracellular apoptotic inhibitory molecules can be targeted by current or new therapeutics to reduce joint damage in RA. However, the therapeutics that target these molecules are yet to reach clinical trial stages. Even so it is evident that understanding the upregulation of anti-apoptotic molecules in RA is required to improve treatments currently available for RA patients.

Keywords

Rheumatoid arthritis Apoptosis Bone erosion Anti-apoptotic proteins Therapeutics Disease-modifying anti-rheumatic drugs 

Abbreviations

AIA

Adjuvant-induced arthritis

AIF

Apoptosis-inducing factor

BIR

Baculovirus inhibitor of apoptosis protein repeats

CAIA

Collagen antibody-induced arthritis

DISC

Death-inducing signalling complex

DMARDs

Disease-modifying anti-rheumatic drugs

FADD

Fas-associated death domain

FLS

Fibroblast-like synoviocytes

FLIP

FLICE-like inhibitory protein

IL

Interleukins

IAP

Inhibitor of apoptosis proteins

NF-κB

Nuclear factor-kappa B

PAPR

Poly ADP-ribose polymerase

RA

Rheumatoid arthritis

RANK

Receptor activator of NF-κB

RANKL

Receptor activator of NF-κB ligand

RIP

Receptor-interacting protein

SMAC

Second mitochondrial activator of caspases

TRAIL

Tumour necrosis factor-related apoptosis-inducing ligand

TRAP

Tartrate-resistant acid phosphatase

TNF-α

Tumour necrosis factor alpha

TUNEL

Transferase dUTP nick end labelling

TRADD

TNF receptor type-1 associated death domain

XIAP

X-linked inhibitor of apoptosis protein

Notes

Acknowledgements

We would like to acknowledge the professional work of Mr. Tavik Morgenstern; Learning and Teaching Officer, University of Adelaide, for his assistance in the preparation of the figure. BW was supported by an Australian Government Research Training Program Scholarship.

Author contributions

BW carried out the literature review, preparing and writing the manuscript with supervision from TC and AD. TC and AD contributed to the writing of the manuscript, discussing the literature and presentation of figures. All authors read and approved the final manuscript.

Compliance with ethical standards

Ethics approval

Not applicable.

Consent for publication

Not applicable.

Availability of data and material

Not applicable.

Conflict of interest

The authors declare that they have no competing interests.

Funding

Not applicable.

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© Springer International Publishing AG, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Adelaide Medical SchoolThe University of AdelaideAdelaideAustralia

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