Synovial tissue analysis of factors related to bone-destruction and bone-production in patients with knee arthritis

Many rheumatic diseases affect the joints. The most common forms of chronic
inflammatory joint disease are rheumatoid arthritis (RA) and a group of
rheumatic diseases collectively known as spondyloarthritis (SpA) which includes
diseases like psoriatic arthritis and ankylosing spondylitis. Treatment of
these inflammatory rheumatic disease with pharmaceutical agents is comparable
with drugs like methotrexate, sulfasalazine and TNF-blockers used in both
diseases.
In both diseases irreversible damage of the joints may develop. In general,
inflammation of joints often leads to premature osteoarthritis. but different
patterns of joint damages occur in RA as compared to SpA and vice versa.
A typical phenomenon observed in RA associated joint destruction is erosion of
bone and cartilage. An erosion of bone in RA is an interruption of the bone
surface caused by invading inflammatory cells.
In contrast, although erosion may also occur SpA the typical pattern of joint
damage in SpA is that of bone deposition. This bone deposition which is the
opposite of bone erosion may lead to ankylosis (fusion of bones) and impairment
of joint mobility.
So while both RA and SpA are both chronic and potentially destructive joint
diseases the way they may damage the joint differs in an extreme way.
Surprisingly , analysis of synovial tissue - soft tissue lining the joint- of
patients with RA and SpA show at first glance more similarities than
differences between the two inflammatory diseases. In both disease there is
proliferation of synovial cells including macrophages and an influx of T-cells
and B-cells. However, RA synovium has a more pronounced intimal lining layer
hyperplasia and more synovial T cells compared with SpA.
So, although both RA and SPA are both inflammatory diseases, clear differences
exist in the inflammation and we propose that these are likely to influence the
outcome of disease in terms of erosions versus bone deposition.
Under physiological circumstances, bone resorption by osteoclasts and bone
formation by osteoblasts are tightly coupled processes. In recent years much
research has been done on how immune cells influence the balance between
osteoclasts and osteoblasts. Most work has been performed on the influence of
immune cells including T-cells and NK-cells on differentiation of monocytes
into osteoclasts and the role of RANKL and TGF in that process in. More
recently mediators produced by macrophages such as BMP and Oncostatin M have
been described to induce differentiation of mesenchymal stem cells into
osteoblasts.

Aim of this study is to obtain synovial tissue and synovial fluid, from 80
patients with non-septic, inflammatory knee arthritis undergoing routine
arthroscopy of the knee and analyze inflammatory factors influencing osteoclast
and osteoblast activation.

The study is a cross-sectional, single centre study.

Arthroscopy as performed by rheumatologists has a low complication rate. In a
recent survey, in which information of 15,682 arthroscopies performed by
rheumatologists was collected, the complication rate was 15.1 per 1000
arthroscopies, which is comparable to the figures reported in the orthopaedic
literature. The arthroscopy nor the taking of excess synovial fluid mentioned
in this protocol is done for study purposes. Only the biopsies performed are
procedures that are done solely for the interest of the study. In the the
previously mentioned study no complications were reported related to the taking
of 2mm biopsies. The synovial fluid collected for this study is waste material
of the arthroscopy.