Advances in the Canine Cranial Cruciate Ligament, 2nd edition

(A) (B)

Figure 13.1 Photomicrographs of frozen sections of (A) synovium and (B) ruptured cranial cruciate ligament (CrCL)
from a 5-year-old dog with cruciate ligament rupture. (A) In this specimen, aggregates of mononuclear cells are present
in the synovial intima (white arrows), including activated macrophages stained red for tartrate-resistant acid phosphatase
(TRAP) (black arrows). (B) In ruptured CrCL from the same dog, aggregates of TRAP+activated macrophages can also be
seen infiltrating the CrCL. TRAP histochemical stain, with Mayer’s hematoxylin counterstain; scale bar= 100 μm. Panel
(A) source: Muiret al.2005. Reproduced with permission from John Wiley & Sons, Inc.

Femur

CaCl

IGFs

IL-8

IL-10

IL-10 IL-8

IL-6

IL-4

CD4+T

MO

AMq

NT

DC CAg

B

PC

C

F

Ab

S

Synovial tissue

Ag presentation

Stimulation

Inhibition

IFN-γ

IFN-γ

IFN-γ

TGF-β

PDGF

bFGF

TGF-β IL-1Ra, sIL-1R,

sTNF-αR

IL-1Ra, sIL-1R,

sTNF-αR

Proliferation

and formation of

joint fibrosis

Joint space

Tibia

Cartilage degradation

Proteinase

Matrix

synthesis

Proteinaseinhibitors IL-1,TNF-α

Figure 13.2 Schematic representation of the possible cytokine cascade in dogs with cruciate ligament rupture (begin at
antigen presentation in the synovial tissue; red lines: stimulation; black lines: inhibition; red boxes: pro-inflammatory;
yellow boxes: anti-inflammatory). Antigen-stimulated dendritic cells present antigens to naive T lymphocytes. Activated
CD4+T lymphocytes can then stimulate different cells (macrophages, monocytes, B lymphocytes, fibroblasts and
synoviocytes) by cytokine release to produce antibodies, osteophytes, ligament degeneration and synovial tissue
proliferation (red lines). Next to the pro-inflammatory reactions, anti-inflammatory responses are seen (black lines). Ab,
antibodies; Ag, antigen; AMq, activated macrophage; B, B lymphocyte; bFGF, basic fibroblast growth factor; C,
chondrocyte; CaCL, caudal cruciate ligament; CAg, collagen antigen; CD4+T, CD4+T lymphocyte; DC, dendritic cell;
IFN-γ, interferon gamma; IGFs, insulin-like growth factors; IL, interleukin; IL-1Ra, interleukin 1 receptor antagonist; F,
fibroblast; Mo, monocyte; NT, na ̈ıve T lymphocyte; PC, plasma cell; PDGF, platelet-derived growth factor; S,
synoviocyte; sIL-1R, soluble IL-1 receptor; sTNF-αR, soluble TNF-αreceptor; TGF-β, transforming growth factor beta;
TNF-α, tumor necrosis factor alpha. Source: Doomet al. 2008. Reproduced with permission from Elsevier.