Effects of treadmill running and limb immobilization on knee cartilage degeneration and locomotor joint kinematics in rats following knee meniscal transection

Abstract

Objective: This study examined the effects of reduced and elevated weight bearing on post-traumatic osteoarthritis (PTOA) development, locomotor joint kinematics, and degree of voluntary activity in rats following medial meniscal transection (MMT). Design: Twenty-one adult rats were subjected to MMT surgery of the left hindlimb and then assigned to one of three groups: (1) regular (i.e., no intervention), (2) hindlimb immobilization, or (3) treadmill running. Sham surgery was performed in four additional rats. Voluntary wheel run time/distance was measured, and 3D hindlimb kinematics were quantified during treadmill locomotion using biplanar radiography. Rats were euthanized 8 weeks after MMT or sham surgery, and the microstructure of the tibial cartilage and subchondral bone was quantified using contrast enhanced micro-CT. Results: All three MMT groups showed signs of PTOA (full-thickness lesions and/or increased cartilage volume) compared to the sham group, however the regular and treadmill-running groups had greater osteophyte formation than the immobilization group. For the immobilization group, increased volume was only observed in the anterior region of the cartilage. The treadmill-running group demonstrated a greater knee varus angle at mid-stance than the sham group, while the immobilization group demonstrated greater reduction in voluntary running than all the other groups at 2 weeks post-surgery. Conclusions: Elevated weight-bearing via treadmill running at a slow/moderate speed did not accelerate PTOA in MMT rats when compared to regular weight-bearing. Reduced weight-bearing via immobilization may attenuate overall PTOA but still resulted in regional cartilage degeneration. Overall, there were minimal differences in hindlimb kinematics and voluntary running between MMT and sham rats.

Articular Cartilage- and Synoviocyte-Binding Poly(ethylene glycol) Nanocomposite Microgels as Intra-Articular Drug Delivery Vehicles for the Treatment of Osteoarthritis

“…This is an interesting observation because cartilage damage seen in the rat MMT model at 6 weeks post-surgery is usually characterized by the development of full-thickness lesions. 45 This observation provides a basis for future evaluation of WYR-functionalized PEG-4MAL nanocomposite microgels and their effect on OA progression. Additionally, synovial membrane thickness as a marker of inflammation was measured via histology image analysis (Figure 5B).…”

“…Although injection of WYR-functionalized PEG-4MAL microgels did not induce a significant reduction in lesion volume compared to free dye and HAP-1-functionalized microgels in MMT rats (Figure F), one of the animals did not exhibit any cartilage lesions and three of them presented smaller lesions than HAP-1 and free dye treated rats. This is an interesting observation because cartilage damage seen in the rat MMT model at 6 weeks post-surgery is usually characterized by the development of full-thickness lesions . This observation provides a basis for future evaluation of WYR-functionalized PEG-4MAL nanocomposite microgels and their effect on OA progression.…”

Gait biomechanics: A clinically relevant outcome measure for preclinical research of musculoskeletal trauma

“…Studies with small animal models of knee PTOA, which include gait analyses as an outcome measure, have mainly used mice 23,57,64,65 and rats 45–51,66 . In general, these studies aim to evaluate the effect of a therapeutic intervention during disease progression.…”

“…43 This review will only discuss mechanically induced methods of the knee as these models are thought to offer the best representation of PTOA sustained by SMs secondary to combatrelated injuries. Preclinical models of mechanically induced PTOA involves either blunt force or surgical insult to the joint structures and includes models such as intra-articular fracture (IAF), 45,46 anterior cruciate ligament (ACL) transection, [47][48][49][50] medial meniscal transection (MMT), 51 ACL reconstruction (ACL-R), 52 destabilization of medial meniscus (D-MM), 53 and lateral meniscectomy (Mx), [54][55][56] to name a few.…”

“…[45][46][47][48][49][50][51]66 In general, these studies aim to evaluate the effect of a therapeutic intervention during disease progression. For example, Tsai et al 51 evaluated the effect of either elevated or reduced weight bearing on cartilage degeneration and locomotor joint kinematics during PTOA progression in a rat model of MMT. Importantly, the study utilized a novel high-speed X-ray motion analysis system to assess kinematic gait alterations of rats running on a treadmill.…”