Early post-traumatic osteoarthritis-like changes in human articular cartilage following rupture of the anterior cruciate ligament

Nelson, Fred R.T.; Billinghurst, R. Clark; Pidoux, I; Reiner, A; Langworthy, Michael J.; McDermott, Mike; Malogne, T.; Sitler, David F; Kilambi, N.R.; Lenczner, Eric; Poole, A. Robin

doi:10.1016/j.joca.2005.08.005

Cited by 147 publications

(115 citation statements)

References 22 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). Decreased chondrocyte density and cell death have now been accepted as hallmarks of OA and have also been suggested as causal factors in the initiation of cartilage degradation (4,5).…”

mentioning

confidence: 77%

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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mentioning

confidence: 77%

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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“…Also it is possible that our dilution methodology, especially when aspirating joint fluid from a normal joint, could have altered the true levels of degradative products and enzymes in our study. In contrast to most other studies analyzing synovial fluid where experimental aspirates are compared with aspirates from different, ''healthy'' control patients, the authors chose to compare the uninjured and injured knees from the same patient to account for any potential biomarker elevation resulting from acute systemic trauma [21,26,30,42,43] . With the patient in the supine position, it is difficult to obtain synovial fluid from the normal knee because the fluid likely collects along the posterior capsule.…”

Section: Discussionmentioning

confidence: 99%

“…In an effort to look specifically at the presence of proteolytic enzymes after traumatic injury, several authors have shown elevated MMPs and aggrecan degradation after ACL tear. However, the time from ACL injury to joint aspiration had considerable variability in these studies [5,7,26,30]. There are currently no human studies of which we are aware that quantify the concentrations of MMPs and/or aggrecan degradation acutely after articular fracture.…”

Section: Introductionmentioning

confidence: 99%

Intraarticular Matrix Metalloproteinases and Aggrecan Degradation Are Elevated After Articular Fracture

Haller

Swearingen

Partridge

et al. 2015

Clin Orthop Relat Res

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Background Posttraumatic osteoarthritis (OA) is a variant of OA that can develop after articular injury. Although the mechanism(s) of posttraumatic OA are uncertain, the presence and impact of postinjury proteolytic enzymes on articular cartilage remain unknown. To our knowledge, there are no studies that evaluate the presence of matrix metalloproteinases (MMPs) or aggrecan degradation after articular fracture.Questions/purposes (1) Are MMP concentrations and aggrecan degradation elevated after intraarticular fracture? (2) Are MMP concentrations and aggrecan degradation greater in high-energy injuries compared with low-energy injuries? (3) Do the concentrations of these biomarkers remain elevated at a secondary aspiration? Methods Between December 2011 and June 2013, we prospectively enrolled patients older than 18 years of age with acute tibial plateau fracture. Exclusion criteria included age older than 60 years, preexisting knee OA, injury greater than 24 hours before evaluation, contralateral knee injury, history of autoimmune disease, open fracture, and non-English-speaking patients. During the enrollment period, we enrolled 45 of the 91 (49%) tibial plateau fractures treated at our facility. Knee synovial fluid aspirations were obtained from both the injured and uninjured knees; two patients received aspirations in the emergency department and the remaining patients received aspirations in the operating room. Twenty patients who underwent spanning external fixator followed by definitive fixation were aspirated during both surgical procedures. MMP-1, -2, -3, -7, -9, -10, -12, and -13 concentrations were quantified using multiplex assays. Aggrecan degradation was quantified using sandwich enzyme-linked immunosorbent assay. Results There were higher concentrations of MMP-1 (3.89 ng/mL [95% confidence interval {CI}, 2.37-6.37] versus 0.37 ng/mL [95% CI, 0.23-0.61], p \ 0.001), MMP-3The institution of one or more of the authors (JMH, TFH) has received peer-reviewed research grant funding from the Orthopedic Trauma Association, LS Peery Foundation, and AO North America for this project. One of the authors certifies that he (TFH), or a member of his immediate family, has signed an agreement with DePuy Synthes (Warsaw, IN, USA) for consulting activities not related to the current study, and has not received payments or benefits, during the study period. One or more of the authors (CAS, KT) are employed at Eli Lilly (Indianapolis, IN, USA). All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research1 editors and board members are on file with the publication and can be viewed on request. Clinical Orthopaedics and Related Research1 neither advocates nor endorses the use of any treatment, drug, or device. Readers are encouraged to always seek additional information, including FDAapproval status, of any drug or device prior to clinical use. Each author certifies that his or her institution approved or waived approval for the reporting of this investigation and that all inves...

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“…It has been well established that women have increased incidence of anterior cruciate ligament (ACL) injuries and that these injuries lead to future osteoarthritis regardless of gender [20,21]. ACL injury often results in a characteristic bone bruise on both the lateral femoral condyle and lateral tibia plateau as demonstrated on MRI.…”

Section: Causes Of Knee Osteoarthritis In Womenmentioning

confidence: 99%

Knee osteoarthritis in women

Hame

Alexander

2013

Curr Rev Musculoskelet Med

163

111

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Osteoarthritis is a disease that progresses over time and culminates in the destruction of articular cartilage and joints. Thus, with an increasing elderly population the treatment of knee osteoarthritis has become a major healthcare issue. It has been shown that women are more severely impacted by knee osteoarthritis. Differences in knee anatomy, kinematics, previous knee injury, and hormonal influences may play a role. Sex difference with respect to osteoarthritis presentation, treatment, and the allocation of resources also exists. In general, women present for treatment in more advanced stages of osteoarthritis and have more debilitating pain than their male counterparts. In addition, healthcare providers are more likely to recommend total joint arthroplasty for their male patients. Understanding how and why these gender differences occur is instrumental in formulating an inclusive strategy for combating osteoarthritis in the future.

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Early post-traumatic osteoarthritis-like changes in human articular cartilage following rupture of the anterior cruciate ligament

Cited by 147 publications

References 22 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

Intraarticular Matrix Metalloproteinases and Aggrecan Degradation Are Elevated After Articular Fracture

Knee osteoarthritis in women

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