Objective To determine the activation of MAP kinases in and around cartilage subjected to mechanical damage and to determine the effects of their inhibitors on impaction induced chondrocyte death and cartilage degeneration. Design The phosphorylation of MAP kinases was examined with confocal microscopy and immunoblotting. The effects of MAP kinase inhibitors on impaction-induced chondrocyte death and proteoglycan loss were determined with fluorescent microscopy and DMMB assay. The expression of catabolic genes at mRNA levels was examined with quantitative real time PCR. Results Early p38 activation was detected at 20 min and 1 hr post-impaction. At 24 hr, enhanced phosphorylation of p38 and ERK1/2 was visualized in chondrocytes from in and around impact sites. The phosphorylation of p38 was increased by 3.0-fold in impact sites and 3.3-fold in adjacent cartilage. The phosphorylation of ERK-1 was increased by 5.8-fold in impact zone and 5.4-fold in adjacent cartilage; the phosphorylation of ERK-2 increased by 4.0-fold in impacted zone and 3.6-fold in adjacent cartilage. Furthermore, the blocking of p38 pathway did not inhibit impaction-induced ERK activation. The inhibition of p38 or ERK pathway significantly reduced injury-related chondrocyte death and proteoglycan losses. Quantative Real-time PCR analysis revealed that blunt impaction significantly up-regulated MMP-13, TNF-α, and ADAMTS-5 expression. Conclusion These findings implicate p38 and ERK MAPKs in the post injury spread of cartilage degeneration and suggest that the risk of PTOA following joint trauma could be decreased by blocking their activities, which might be involved in up-regulating expressions of MMP-13, ADAMTS-5, and TNF-α.

Instability is a significant concern in total hip arthroplasty, particularly when there is structural compromise of the capsule due to pre-existing pathology or due to necessities of surgical approach. An experimentally grounded fiber-direction-based finite element model of the hip capsule was developed, and was integrated with an established three-dimensional model of impingement/dislocation. Model validity was established by close similarity to results from a cadaveric experiment in a servohydraulic hip simulator. Parametric computational runs explored effects of graded levels of capsule thickness, of regional detachment from the capsule’s femoral or acetabular insertions, of surgical incisions of capsule substance, and of capsule defect repairs. Depending strongly upon the specific site, localized capsule defects caused varying degrees of construct stability compromise, with several specific situations involving over 60% decrement in dislocation resistance. Construct stability was returned substantially toward intact-capsule levels following well conceived repairs, although the suture sites involved were often at substantial risk of failure. These parametric model results underscore the importance of retaining or robustly repairing capsular structures in total hip arthroplasty, in order to maximize overall construct stability.

Background Impingement events, in addition to their role immediately proximate to frank dislocation, hold the potential to damage new-generation hard-on-hard bearings as a result of the relatively unforgiving nature of the materials and designs. Because of the higher stiffness and tighter design tolerances of metal-on-metal and ceramic implants, surgical positioning plausibly has become even more important. Questions/purposes We asked (1) whether, and under what cup orientation conditions, hard-on-hard impingements might challenge implant material failure strength; and (2) whether particle generation propensity at impingement and egress sites would show similar dependence on cup orientation. Methods Realistic computational simulations were enabled by multistage finite element analyses, addressing both global construct motion and loading, and focal stress concentrations at neck impingement and rim egress sites. The global model, validated by a cadaveric simulation in a servohydraulic hip simulator, included both hardware components and advanced anisotropic capsule characterization. Parametric computational runs explored the effect of cup orientation for both ceramic-on-ceramic and metalon-metal bearing couples for two distinct motion sequences associated with dislocation.

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