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Role of Synovial Immune

Responses in Stifle Synovitis

Peter Muir

Introduction

The historical paradigm for the cruciate liga-
ment rupture (CR) mechanism has been that
ligament rupture is largely a consequence of
trauma, with arthritis developing secondary to
joint instability. However, a growing body of
evidence suggests that this relationship is incor-
rect, and that in dogs with naturally occurring
CR, synovitis and arthritis typically precede the
development of complete ligament rupture and
associated stifle instability. In dogs with CR,
epidemiological studies suggest that if subtle
radiographic change is present in the contralat-
eral stifle, the risk of contralateral rupture at 16
months is as high as 65% (Doverspikeet al. 1993;
Chuanget al. 2014). Whilst it is clear that cranial
cruciate ligament (CrCL) transection and asso-
ciated stifle instability contributes to the devel-
opment of synovitis (Lipowitzet al. 1985), the
growing use of arthroscopy for stifle evaluation
in the dog, and the use of tibial plateau level-
ing osteotomy surgery to treat dogs with partial
CR and a stable stifle, has led to a greater appre-
ciation that synovitis is present in stable stifles
of affected dogs (Bleedornet al. 2011). The cru-
ciate ligaments are intra-articular, but extrasyn-
ovial, and are covered in synovium. Experimen-
tally, persistent synovitis induces a substantial

degradation of CrCL tensile strength (Goldberg

et al. 1982). The deleterious effects of chronic

joint inflammation on the tissue matrix of the

cruciate ligaments is likely due to disruption

of the blood–cruciate barrier in the ligament

microvasculature, such that cruciate ligament

metabolism is closely related to changes in syn-

ovial fluid (Kobayashiet al. 2006).

A logical extension of this shift in thinking

is to focus on understanding the disease mech-

anism that leads to the development of sti-

fle synovitis in dogs. Current evidence sug-

gests that synovial immune responses promote

progressive degradation of intra-articular struc-

tures over time, including the cruciate liga-

ments (Doomet al. 2008).

Inflammatory cell populations within

the stifle joint

Synovitis involves the intima of the CrCL

epiligament. The inflammatory cell popula-

tion is typically a mixed mononuclear one,

and includes activated tartrate-resistant acid

phosphatase-positive (TRAP) macrophages

(Figure 13.1), T and B lymphocytes (Fig-

ure 13.2), plasma cells, and major histocom-

patibility complex (MHC) class II-positive

Advances in the Canine Cranial Cruciate Ligament, Second Edition. Edited by Peter Muir. © 2018 ACVS Foundation.
This Work is a co-publication between the American College of Veterinary Surgeons Foundation and Wiley-Blackwell.

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