Influence of Knee Immobilization on Chondrocyte Apoptosis and Histological Features of the Anterior Cruciate Ligament Insertion and Articular Cartilage in Rabbits

Abstract

This study examined the influence of immobilization on chondrocyte apoptosis and histological features of the anterior cruciate ligament (ACL) insertion and knee articular cartilage in rabbits. Forty-eight male Japanese white rabbits were assigned to an immobilization (n = 24) or sham (n = 24) group. Rabbits in the immobilization group underwent complete unilateral surgical knee immobilization and rabbits in the sham group underwent a sham surgery. The average thickness of the glycosaminoglycan (GAG) stained red area by safranin O staining, the chondrocyte apoptosis rate and the chondrocyte proliferation rate in the cartilage layer in the ACL insertion and the articular cartilage of the medial tibial condyle were measured at one, two, four and eight weeks in six animals from each group. In the ACL insertion, the chondrocyte apoptosis rate was higher in the immobilization group than in the sham group at two and eight weeks after surgery (p < 0.05). The chondrocyte proliferation rate gradually decreased from two weeks to eight weeks in the immobilization group. The GAG layer was thinner in the immobilization group than in the sham group at two, four and eight weeks after surgery (p < 0.05). In the articular cartilage, the chondrocyte apoptosis rate in the immobilization group was higher than in the sham group at four and eight weeks after surgery (p < 0.05). The GAG layer was significantly thinner in the immobilization group than that in the sham group at four and eight weeks after surgery (p < 0.05). Knee immobilization significantly increased chondrocyte apoptosis at two and eight weeks after surgery in the ACL insertion and at four and eight weeks after surgery in the articular cartilage of the medial tibial condyle, and decreased GAG layer thickness from two to eight weeks after surgery in the ACL insertion and from four to eight weeks after surgery in the articular cartilage.

Impact of exercise on articular cartilage in people at risk of, or with established, knee osteoarthritis: a systematic review of randomised controlled trials

“…High-impact activities (eg, jumping)30 and participation in sports15 is associated with cartilage deformation and increased risk of radiographic OA. Similarly, lack of knee joint loading in the form of knee immobilisation31 or sedentary behaviour19 20 is associated with detrimental cartilage changes. Therefore, interventions including activities being considered outside the therapeutic loading spectrum were assessed as inadequate to promote cartilage health.…”

A Preclinical Model to Study the Influence of Graft Force on the Healing of the Anterior Cruciate Ligament Graft

“…Joint immobilization in those models also limits the ability to evaluate other intra-articular structures since prolonged immobilization leads to deterioration of cartilage surfaces. [23][24][25] Our current research model more closely approximates what occurs in human clinical scenarios.…”

Extension of knee immobilization delays recovery of histological damages in the anterior cruciate ligament insertion and articular cartilage in rabbits

“…After intravenous barbiturate injection (40 mg/kg), the remobilization group underwent right knee internal fixation using a method similar to that described previously 10 ) . After 1, 2, 4 and 8 weeks respectively, (n=6 animals in each subgroup according to the period of immobilization), the fixation devices were removed and the rabbits moved freely for 8 weeks; after 8 weeks, all six animals in each subgroup were euthanized.…”

“…The ACL insertions and articular cartilages of the medial tibial condyle from each animal were fixed in neutral-buffered formalin, decalcified and embedded in paraffin 10 , 16 , 17 ) . The specimens were stained with hematoxylin and eosin and safranin O 10 , 16 , 17 ) . Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling (TUNEL) was performed to detect apoptotic cells ( Fig.…”

“…Immobilization-induced articular cartilage degeneration is caused by decreases in the number of chondrocytes and cartilage extracellular matrix (ECM), changes in cartilage thickness, upregulation of destructive factors in the ECM, and cartilage surface alterations 5 , 6 , 7 , 8 , 9 ) . We previously reported that knee immobilization in rabbits resulted in an increase in chondrocyte apoptosis at 2 and 8 weeks in the ACL insertion and at 4 and 8 weeks in the articular cartilage of the medial tibial condyle, and a decrease in safranin O-stained glycosaminoglycan (GAG) layer thickness from 2 to 8 weeks in the ACL insertion and from 4 to 8 weeks in the articular cartilage 10 ) .…”