Sports, Joint Injury, and Posttraumatic Osteoarthritis

Buckwalter, Joseph A.

doi:10.2519/jospt.2003.33.10.578

Cited by 160 publications

(157 citation statements)

References 79 publications

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“…The development of OA is associated with high-impact sports, which supports the idea that mechanical stress is a major initiator of OA (2). Initially, loss of proteoglycans and of collagen network integrity occur (3).…”

supporting

confidence: 49%

Calcium signaling leads to mitochondrial depolarization in impact‐induced chondrocyte death in equine articular cartilage explants

Huser¹,

Davies²

2007

Arthritis & Rheumatism

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Objective. Chondrocyte apoptosis is an important factor in the progression of osteoarthritis. This study aimed to elucidate the mechanisms involved upstream of caspase 9 activation and, in particular, calcium signaling and mitochondrial depolarization.Methods. Articular cartilage explants obtained from healthy horses were subjected to a single impact load (500-gm weight dropped from a height of 50 mm) and cultured in vitro for up to 48 hours. Chondrocyte death was quantified by the TUNEL method. Release of proteoglycans was determined by the dimethylmethylene blue assay. Weight change was measured, and mitochondrial depolarization was determined using JC-1 staining. To assess the role of calcium signaling in impact-induced chondrocyte death, explants were preincubated in culture medium containing various concentrations of calcium. Inhibitors were used to assess the role of individual signaling components in impactinduced chondrocyte death.Results. Calcium quenching, inhibitors of calpains, calcium/calmodulin-regulated kinase II (CaMKII), and mitochondrial depolarization reduced impact-induced chondrocyte death after 48 hours in culture. Transient mitochondrial depolarization was observed 3-6 hours following a single impact load. Mitochondrial depolarization was prevented by calcium quenching, inhibitors of calpain, CaMKII, permeability transition pore formation, ryanodine receptor, and the mitochondrial uniport transporter. Cathepsin B did not appear to be involved in impact-induced chondrocyte death. The calpain inhibitor prevented proteoglycan loss, but the percentage weight gain and proteoglycan loss were unaffected by all treatments used.Conclusion. Following a single impact load, calcium is released from the endoplasmic reticulum via the ryanodine receptor and is taken up by the mitochondria via the uniport transporter, causing mitochondrial depolarization and caspase 9 activation. In addition, calpains and CaMKII play important roles in causing mitochondrial depolarization.

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supporting

confidence: 49%

Calcium signaling leads to mitochondrial depolarization in impact‐induced chondrocyte death in equine articular cartilage explants

Huser¹,

Davies²

2007

Arthritis & Rheumatism

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“…5 Prior knee injury is a known risk factor for OA development. 9 Altered biomechanics, such as changes in joint alignment, ligamentous laxity, or deficient proprioception, may all lead to OA after injury. 10 Alterations in surface friction, possibly due to inflammatory destruction of synovial fluid lubricants and altered cartilage tissue properties, may also contribute to the onset of disease.…”

Section: Introductionmentioning

confidence: 99%

Coefficients of friction, lubricin, and cartilage damage in the anterior cruciate ligament‐deficient guinea pig knee

Teeple

Elsaid

Fleming

et al. 2007

Journal Orthopaedic Research

106

102

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The coefficient of friction (COF) of articular cartilage is thought to increase with osteoarthritis (OA) progression, and this increase may occur due to a decrease in lubricin concentration. The objectives of this study were to measure the COF of guinea pig tibiofemoral joints with different stages of OA and to establish relationships between COF, lubricin concentrations in synovial fluid, and degradation status using the Hartley guinea pig model. Both hind limbs from 24 animals were harvested: seven 3-month-old (no OA), seven 12-month-old (mild OA), and 10 that were euthanized at 12 months of age after undergoing unilateral ACL transection at 3 months of age (moderate OA). Contralateral knees served as age-matched controls. COFs of the tibiofemoral joints were measured using a pendulum apparatus. Synovial fluid lavages were analyzed to determine the concentration and integrity of lubricin using ELISA and Western blot, and the overall articular cartilage status was evaluated by histology. The results showed that the mean COF in the ACL-deficient knees was significantly greater than that of the no OA (p < 0.01) and mild OA knees (p < 0.01). Lubricin concentrations in the ACL-deficient knees were significantly lower than that in both of the other groups (p < 0.01). No significant differences in COF or lubricin concentration were found between the no OA and mild OA knees. Histology verified the extent of cartilage damage in each group. ß

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“…The etiology of posttraumatic osteoarthritis is complex and multifactorial 35 , affected not only by chronic biomechanical residuals but also by acute to subacute cartilage damage at the time of injury and its subsequent propagation by biological stimuli. While it is unknown under what circumstances any of these factors dominate the progression from injury to posttraumatic osteoarthritis, the results of the present investigation support current treatment paradigms that prioritize restoring stability to acutely injured joints.…”

mentioning

confidence: 99%

Instability Dependency of Osteoarthritis Development in a Rabbit Model of Graded Anterior Cruciate Ligament Transection

Tochigi

Vaseenon

Heiner

et al. 2011

Journal of Bone and Joint Surgery

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Sports, Joint Injury, and Posttraumatic Osteoarthritis

Cited by 160 publications

References 79 publications

Calcium signaling leads to mitochondrial depolarization in impact‐induced chondrocyte death in equine articular cartilage explants

Calcium signaling leads to mitochondrial depolarization in impact‐induced chondrocyte death in equine articular cartilage explants

Coefficients of friction, lubricin, and cartilage damage in the anterior cruciate ligament‐deficient guinea pig knee

Instability Dependency of Osteoarthritis Development in a Rabbit Model of Graded Anterior Cruciate Ligament Transection

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