Progressive Chondrocyte Death After Impact Injury Indicates a Need for Chondroprotective Therapy

Abstract

Background Impact injury to articular cartilage can lead to posttraumatic osteoarthritis. Hypotheses This study tests the hypotheses that (1) chondrocyte injury occurs after impact at energies insufficient to fracture the cartilage surface, and that (2) cartilage injury patterns vary with impact energy, time after injury, and cartilage thickness. Study Design Controlled laboratory study. Methods Fresh bovine osteochondral cores were randomly divided into 5 groups: (1) control, (2) 0.35 J, (3) 0.71 J, (4) 1.07 J, and (5) 1.43 J impact energies. Cores were subjected to computer-controlled impact loading and full-thickness sections were then prepared and incubated in Dulbecco's Modified Eagle's Medium/F12 at 37°C. Adjacent sections were harvested 1 and 4 days after impact for viability staining and fluorescent imaging. The area of dead and living chondrocytes was quantified using custom image analysis software and reported as a percentage of total cartilage area. Results The highest impact energy fractured the cartilage in all cores (1.43 J, n = 17). Seventy-three percent and 64% of the osteochondral cores remained intact after lower energy impacts of 0.71 J and 1.07 J, respectively. At lower energy levels, fractured cores were thinner (P < .01) than those remaining intact. In cores remaining intact after impact injury, chondrocyte death increased with increasing impact energy (P < .05) and with greater time after impact (P < .05). A progressive increase in dead cells near the bone/cartilage interface and at the articular surface was observed. Conclusion These data showing progressive chondrocyte death after impact injury at energies insufficient to fracture the cartilage surface demonstrate a potential need for early chondroprotective therapy. Clinical Relevance These data show that efforts to reduce chondrocyte morbidity after joint injury may be a useful strategy to delay or prevent the onset of posttraumatic osteoarthritis.

Melanocortin peptides protect chondrocytes from mechanically induced cartilage injury

“…Traumatic joint injuries are a major risk factor for the development and progression of OA [2] and increase the risk of arthritis 5 to 17-fold [3,4]. Knee traumas, in particular, represent over 40% of all sports injuries [5][6][7] and often result from traffic accidents with surgical restoration of joint stability not preventing future arthritis development [8][9][10][11].…”

“…Knee traumas, in particular, represent over 40% of all sports injuries [5][6][7] and often result from traffic accidents with surgical restoration of joint stability not preventing future arthritis development [8][9][10][11]. The incidence of post-traumatic arthritis is therefore high -creating insistent demand for pharmacological intervention, directed at limiting the progression and propagation of destructive processes taking place in the early stages post-injury [2,12].…”

Osteoarthritis: From Palliation to Prevention

“…Cellular and molecular targets for intervention include administration of chondro-resuscitative substances such as growth factors, anti-apoptotic treatments, free radical scavengers, and anti-inflammatory agents 13,14 . In vitro studies suggest that there is a role for acute treatment after impact injury to articular cartilage when progressive chondrocyte death and apoptosis have been observed within minutes to days 13,15 . In particular, brief exposure to free radical scavengers (e.g., rotenone) two hours after an impact injury has been shown to reduce oxidative stress and prevent chondrocyte death 13 .…”

A Sex-Stratified Multivariate Risk Factor Model for Anterior Cruciate Ligament Injury

“…This approach does not take into consideration that the ACL injury itself is capable of producing both shortterm and long-term changes in knee-joint geometry. 1,5 Furthermore, few investigators have used measurement techniques with established interobserver and intraobserver measurement reliability.10 Finally, many researchers have evaluated men and women as a combined group. However, in light of the disparities that exist between the sexes in ACL injury rates, knee-joint geometry, anatomical alignment, joint laxity, demographic characteristics, and strength, male and female models of injury risk should be considered separately.…”

“…[1][2][3][4][5][6][7][8] Regardless of whether a patient chooses surgical or nonsurgical treatment, ACL injury is associated with the onset of posttraumatic arthritis. 9 Consequently, recent researchers have focused on understanding the mechanisms and factors that place individuals at increased risk for sustaining this severe injury.…”