Synovitis Precedes Stifle Instability Associated with Cruciate Ligament Rupture 95(A)300 μm 100 μm(B)Figure 12.3 Biopsy specimens from dog with complete cranial cruciate ligament rupture. (A) There is marked cellular
infiltration and lymphoid nodule formation resulting in expansion of the synovial intimal margin. (B) Higher magnification
of the area designated by the box in panel (A) demonstrates a focal region of predominantly mononuclear cell
infiltration. Frozen section with hematoxylin and eosin stain. Low magnification, scale bar= 300 μm; high magnification,
scale bar= 100 μm. Source: Bleedornet al. 2011. Reproduced with permission from John Wiley & Sons, Inc.
tissues of dogs with CR. The synovial fluid
contains immune complexes and antibodies
to collagen types I and II (Neibauer & Menzel
1982; de Roosteret al. 2000; de Bruinet al. 2007).
The inflamed synovial membrane contains
mononuclear infiltrate and, at times, nodular
lymphoplasmacytic aggregates (Galloway
& Lester 1995). Activated B and T lympho-
cytes and major histocompatibility complex
class II antigen-positive cells with a dendritic
morphology are also typically found. These
cell populations are similar to those found in
erosive immune-mediated polyarthritis, albeit
at lower levels (Lemburg et al. 2004; Muir
et al. 2005; Muiret al. 2011). Collectively, these
changes reflect the substantial inflammatory
changes that develop in stifle synovial tissues
of dogs with CR.
Synovitis is believed to contribute to the
development of pain, joint inflammation and
the progression of OA (Sutton et al. 2009).
Pro-inflammatory cytokines synthesized in the
synovium potentiate the cascade of biologically
active substances that contribute to degrada-
tion of the joint (Doomet al. 2008). Synovial
macrophages, the main promoters of disease
activity in human rheumatoid arthritis, may
have a similar role in OA (Bondesonet al. 2006).
Synovial macrophage numbers are increased
in the joint capsule of dogs with CR, and are
associated with the severity of OA (Klocke
et al. 2005). Furthermore, macrophage-like cells
in the synovium produce matrix-degradative
enzymes (Muiret al. 2005). It is likely this
hostile environment results in the progression
of OA and may have deleterious effects on
cranial cruciate ligament (CrCL) homeostasis.
Use of the canine stifle as a translational
model for OA research provides useful infor-
mation regarding the pathogenesis of CR.
Experimental CrCL transection leads to joint
instability, synovitis, and osteophyte forma-
tion (Gardneret al. 1984; Lipowitzet al. 1985;
Myerset al. 1990). Similarly, the induction of an
immune synovitis results in a significant reduc-
tion in CrCL strength and leads to structural
failure and mid-substance rupture (Goldberg
et al. 1982). Decades ago, Arnoczky and oth-
ers eloquently showed that the synovium
provides a vigorous and extensive vascular
response to iatrogenic cruciate injury, which is
decreased with synovial resection (Arnoczky
et al. 1979). Recent evidence in a canine model
demonstrated that synovial debridement alone
leads to joint effusion, pain, lameness, and
compromised clinical function, comparable
to partial cruciate resection (Bozynski et al.
2015). Stifle radiographic arthritis and cruciate