Periarticular ligament changes following ACL/MCL transection in an ovine stifle joint model of osteoarthritis

Abstract

Anterior cruciate ligament (ACL) injuries often lead to significant functional impairment, and are associated with increased risk for induction of degenerative joint disease. However, few studies have described the effect of ligament transection on the remaining intact knee ligaments. This study sought to determine specifically what impact combined ACL/medial collateral ligament (MCL) transection had on the remaining intact knee ligaments, particularly from the histological, biochemical, and molecular perspectives. Twenty weeks post-ACL/MCL transection, the cut ends of sheep MCLs were bridged by scar, while the posterior cruciate ligaments (PCLs) and lateral collateral ligaments (LCLs) seemed gross morphologically normal. Water content and cell density increased significantly in the MCL scars and the intact PCLs but were unchanged in the LCLs. Collagen fibril diameter distribution was significantly altered in both MCL scar tissue and uninjured PCLs from transected joints. MMP-13 mRNA levels in MCL scars and PCLs from ligament transected joints were increased, while TIMP-1 mRNA levels were significantly decreased in the PCLs only. This study has shown that some intact ligaments in injured joints are impacted by the injury. The joint appears to behave like an integrated organ system, with injury to one component affecting the other components as the ''organ'' attempts to adapt to the loss of integrity. ß

ACL/MCL transection affects knee ligament insertion distance of healing and intact ligaments during gait in the Ovine model

“…At 20 weeks after ACL/MCL transection, the cut ends of the ACL remained separate, but the cut ends of the MCL were bridged by scar (Funakoshi et al, 2007). Hypotheses to explain the differential healing capacity of the ACL and MCL include differences in blood supply (Bray et al, 2003a), vascular and metabolic response to injury (Bray et al, 2003a;Nagineni et al, 1992), and intra-articular vs. extra-articular location (Spindler et al, 2006).…”

“…A small number of studies have demonstrated that ACL deficiency results in biological changes in adjacent ligaments (Funakoshi et al, 2007;Zachos et al, 2002). At 20 weeks after ACL/MCL transection, the cut ends of the ACL remained separate, but the cut ends of the MCL were bridged by scar (Funakoshi et al, 2007).…”

Carrageenan-induced transient inflammation in a rabbit knee model: molecular changes consistent with an early osteoarthritis phenotype

“…Currently, there is an increasing interest in the early detection of OA in order to possibly slow and/or stop its progression. Most animal model studies have demonstrated a delayed development of OA after severe injuries to the joint [24][25][26]. The degeneration of cartilage is a slow process and is observed only after 20 weeks following anterior cruciate ligament (ACL)/ medial collateral ligament (MCL) transection in an ovine model.…”

Temporal extracellular matrix adaptations in ligament during wound healing and hindlimb unloading

“…Biochemical analyses were conducted of 1) hydroxyproline (Hyp), an imino acid marker used as an index of total collagen content measured by HPLC, 2) the mature collagen cross-link hydroxylysylpyridinoline (HP), which improves ECM strength and tissue quality in healing ligaments, also measured by HPLC, and 3) MCL cellularity by DNA measurement to assess the state of cell proliferation in the healing ligament. Real-time quantitative PCR gene markers were used to determine the upregulation or downregulation of specific genes that impact the ECM in healing MCLs as previously determined (15,18,19,32,34). To assess new collagen synthesis in remodeling ligament, the genes encoding collagen type I (Col1A2), collagen type III (Col3A1), and collagen type V (Col5a1) were assayed.…”