Page 845 - Adams and Stashak's Lameness in Horses, 7th Edition

Principles of Musculoskeletal Disease 811

Activators Fibroblasts
VetBooks.ir Trauma and inflammation Macrophage

Neutrophil
IL1
TNF
Lymphocyte
Synoviocyte

Synovial membrane Prostaglandins

IGF-1 Metalloproteinases Free radicals
Aggrecanase IL1 FGF-2 • Stromelysin Wear
TNF TGF- • Collagenase particles
Synovial Trauma BMPs • Gelatinase Hyaluronan
fluid degradation

Articular
cartilage
Chondrocytes Serine proteinase
Serine proteinases inhibitor
uPA tPA
(PA inhibition)
Metalloproteinases
Plasminogen
PGE 2
Latent stromelysin activator
Latent collagenase
Plasmin Plasminogen
Active Active stromelysin
collagenase
Cysteine
TIMP Matrix degradation proteinases
(cathepsin B)

Physical damage IL1
TNF
Trauma Bone resorption
Subchondral bone Inflammation

Figure 7.9. Factors involved in degradation of the articular (PA), insulin‐like growth factor‐1 (IGF‐1), transforming growth
matrix: interleukin‐1, tumor necrosis factor‐α (TNFα), fibroblast factor‐β (TGF‐β), and bone morphogenic protein (BMP). Source:
growth factor‐2 (FGF‐2), PLA2, urokinase plasminogen activator Redrawn from figure 5, McIlwraith. Reproduced with permission of
64
(uPA), tissue plasminogen activator (tPA), plasminogen activator American Association of Equine Practitioners.

of significance in equine joint disease include metallo­ MMP‐13). Based on evidence in both human and equine
proteinases and aggrecanases, prostaglandins, free radi­ studies, it appears that the primary collagenase involved
cals, cytokines, interleukin‐1 (IL‐1), and possibly TNFα in the degradation of type II collagen of articular carti­
(Figure 7.9). lage is collagenase 3. 10,70 Caron et al. found that MMP‐13
is produced by equine chondrocytes and that MMP‐13
expression was significantly stimulated by rhIL‐1. 10
Matrix Metalloproteinases and Aggrecanases
Consideration of the breakdown of aggrecan initially
Matrix metalloproteinases (MMPs) may be subdivided focused on stromelysin (also called proteoglycanase or
into collagenases, gelatinases, and stromelysins. Three MMP‐3), but now recognizes an initially undefined enzyme
collagenases have been identified, and they are intersti­ called “aggrecanase” (now known as aggrecanase‐1
tial or tissue collagenase (also called MMP‐1), PMN col­ and aggrecanase‐2 or ADAMTS‐4 and ADAMTS‐11).
lagenase (or MMP‐8), and collagenase 3 (also known as Stromelysin has a wide variety of substrates, including