Complementary models reveal cellular responses to contact stresses that contribute to post‐traumatic osteoarthritis

Abstract

Two categories of joint overloading cause post-traumatic osteoarthritis (PTOA): single acute traumatic loads/impactions and repetitive overloading due to incongruity/instability. We developed and refined three classes of complementary models to define relationships between joint overloading and progressive cartilage loss across the spectrum of acute injuries and chronic joint abnormalities: explant and whole joint models that allow probing of cellular responses to mechanical injury and contact stresses, animal models that enable study of PTOA pathways in living joints and pre-clinical testing of treatments, and patient-specific computational models that define the overloading that causes OA in humans. We coordinated methodologies across models so that results from each informed the others, maximizing the benefit of this complementary approach. We are incorporating results from these investigations into biomathematical models to provide predictions of PTOA risk and guide treatment. Each approach has limitations, but each provides opportunities to elucidate PTOA pathogenesis. Taken together, they help define levels of joint overloading that cause cartilage destruction, show that both forms of overloading can act through the same biologic pathways, and create a framework for initiating clinical interventions that decrease PTOA risk.

Targeting mitochondrial responses to intra-articular fracture to prevent posttraumatic osteoarthritis

“…This experiment represented an ideal situation in which the minipigs received treatment within an hour after injury; however, delivery vehicles are available that would allow clinical delivery of amobarbital or NAC before surgical fixation (42). Our foundational studies suggest that targeting this pathway is effective when applied within 4 hours of the initial injury (43), but a therapeutic window must be determined in human applications where all of the appropriate clinical variables are present. Thus, human investigation is necessary for more detailed parameters for dosing (timing, number of injections, and volume of injections).…”

Management of Posttraumatic Ankle Arthritis: Literature Review

“…Weight-bearing radiographs with AP, lateral, and mortise views are generally recommended for initial imaging. PTAA may be evidenced on radiography via joint space narrowing, osteophytes, and subchondral bone sclerosis [2,3] 80% prevalence in ages > 55 [2,3] Female sex [4,5] Relative risk of 2.6 [5] Higher rates of rapid structural damage [6] Obesity/metabolic syndrome One of the strongest modifiable risk factors [5,6] Repetitive overloading of cartilage ➔ chondrocyte oxidant-dependent mitochondrial dysfunction ➔ disruption of chondrocyte anabolic responses to mechanical stimuli ➔ cartilage destabilization [7] Higher bone mineral density Especially related to hip OA in older women [8][9][10] Conflicting evidence in regard to the relationship between estrogen replacement therapy and OA Occupation Sports activities [11] Recreational parachuting (ankle) Ballet dancing (talar joints) Soccer (ankle, talar joints) Football (foot/ankle)…”

“…Both tissue injury incurred in the acute setting and the resultant structural abnormalities in the ankle contribute to the development of ankle instability and joint surface incongruity; the two primary mechanisms responsible for the loss of articular cartilage, bone remodeling, and degenerative changes which define OA. Alteration of ankle biomechanics, in turn, alters the mechanical loading of the ankle joint, which ultimately produces a mechanically driven degenerative remodeling process [6,7].…”

What’s New in Orthopaedic Basic Science

“…Martin et al have recommended the use of sub-classification in their work on the development of predictive models for PTOA 5 . They have identified three broad categories of models that can be used to examine the interactions between mechanical overloading and cartilage loss.…”