Inflammation Research

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

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



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.


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



Adjuvant-induced arthritis


Apoptosis-inducing factor


Baculovirus inhibitor of apoptosis protein repeats


Collagen antibody-induced arthritis


Death-inducing signalling complex


Disease-modifying anti-rheumatic drugs


Fas-associated death domain


Fibroblast-like synoviocytes


FLICE-like inhibitory protein




Inhibitor of apoptosis proteins


Nuclear factor-kappa B


Poly ADP-ribose polymerase


Rheumatoid arthritis


Receptor activator of NF-κB


Receptor activator of NF-κB ligand


Receptor-interacting protein


Second mitochondrial activator of caspases


Tumour necrosis factor-related apoptosis-inducing ligand


Tartrate-resistant acid phosphatase


Tumour necrosis factor alpha


Transferase dUTP nick end labelling


TNF receptor type-1 associated death domain


X-linked inhibitor of apoptosis protein



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.


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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