Hypothesis 1b—trauma to the stifle joint 

Often stifle injury is associated with a rupture of on or more of the ligaments.  Most 
commonly the anterior cruciate ligament (ACL) is involved.  The cruciate ligaments 
assist with the collateral ligaments in opposing lateral or medial deviation of the leg.  
While complete rupture of the ACL would result in a positive cranial drawer sign, a 
partial rupture (only some fibers torn) may be missed in this test.  In most cases there is 
pain, swelling and inflammation followed often by complete rupture of the ligament. 
Often partial or complete rupture is followed by the deposition of fibrous tissue around 
the joint in order to provide some means of stability. This effect is known as buttressing.  
As a result the joint capsule is thickened, the animal is painful or intermittently painful 
and lame or intermittently lame. Often the meniscus of the knee joint will become 
damaged and result in a broken segment when the ACL is ruptured. This will cause pain 
and further damage to the joint. 
As a result of the damaged ligament(s) it is possible that there may be inappropriate 
alignment of joint structures, inflammation then degenerative changes, including the 
further weakening of the ligamentous supports in the stifle.  It is possible that without 
correction osteoarthritis may occur. This is characterized by slow changes in matrix 
metabolism. Initially there is an increase in the water content of cartilage leading to a 
failure in the elastic restraint of the collagen network. Shortly afterward, an increased 
turnover of proteoglycans occurs leading to an eventual net loss of cartilage matrix as 
catabolic events dominate over anabolic events.  There are numerous biochemical factors 
that play a role in the depletion of the cartilage matrix process cytokines (interleukins-1, 
6, and 8) and tumor necrosis factor alpha (TNF-a).  The resulting consequences are an 
eventual remodeling of the bone, joint capsule damage, muscle weakness, and pain.