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Advances in
bone biology may lead to improved RA therapy
What is the problem and
what is already known?
Rheumatoid arthritis is characterized by chronic inflammation
that can lead to destruction of the bone and cartilage in the joint and
ultimately, to joint deformities and loss of function. Existing evidence
suggests that certain cells called osteoclasts
play an important role in bone destruction in RA. Researchers have
found that a cytokine (an
inflammatory chemical) called RANKL is essential to the development and
activation of osteoclasts and that the biological effects of RANKL are
normally balanced by an antagonist protein called osteoprotegerin (OPG).
As described in two recent publications, current studies are continuing
to provide insights about the role of osteoclasts, RANKL and OPG in RA
bone destruction.
Researchers funded by the Arthritis Foundation involved in the
studies: Ellen
Gravallese, MD & Allison Pettit, MD, Beth Israel Deaconess Medical
Center, Harvard Institutes of Medicine, Boston
Who was studied and what
was done?
These studies used different mice models that simulated RA-like
disease. One study also utilized mice that were specially bred and
lacked RANKL. 
What were the study results?
Several key discoveries that advance our understanding of bone
destruction in RA were made. It was learned that cells are present in
the joint lining tissue called the synovium
that have receptor molecules called “RANK” on their surface. These
cells have the potential to evolve into osteoclasts when RANKL binds to the RANK receptor on their
surface. An experiment with mice that had arthritis but lacked RANKL
showed that these mice developed
cartilage damage but had greatly reduced bone damage compared to
arthritic control mice that expressed RANKL. These studies support the
theory that in mice with RA-like disease, osteoclasts and the RANK/
RANKL pathway play an important role in bone loss. Moreover, the mechanisms that
lead to bone destruction are distinct from those that lead to cartilage
destruction. Further
research is needed to determine if these findings also apply to humans
and if there are other relevant cells and cytokines involved in the
process of bone erosion.
What’s the relevance to
people with arthritis?
Documenting that there is a distinct pathway that contributes to
bone loss may lay the basis for new types of therapeutic approaches for
arthritis. According to Dr. Gravallese, “The role of the osteoclast as
a cell type that contributes to bone erosion in arthritis allows for the
possibility that therapies targeting osteoclasts, either directly or
indirectly, may be of benefit in conjunction with anti-inflammatory
therapies to help protect RA patients from bone destruction.”
Source: Arthritis
and Rheumatism, November 2002 & Annals of Rheumatic Disease,
November 2002
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12428250&dopt=Abstract
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12379632&dopt=Abstract
 
Research Update is compiled by
Michele Boutaugh, BSN, MPH, Medical and Scientific Affairs Department,
National Office.
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