Regulation of the Catabolic Cascade in Osteoarthritis by the Zinc-ZIP8-MTF1 Axis

SummaryOsteoarthritis (OA), primarily characterized by cartilage degeneration, is caused by an imbalance between anabolic and catabolic factors. Here, we investigated the role of zinc (Zn2+) homeostasis, Zn2+ transporters, and Zn2+-dependent transcription factors in OA pathogenesis. Among Zn2+ transporters, the Zn2+ importer ZIP8 was specifically upregulated in OA cartilage of humans and mice, resulting in increased levels of intracellular Zn2+ in chondrocytes. ZIP8-mediated Zn2+ influx upregulated the expression of matrix-degrading enzymes (MMP3, MMP9, MMP12, MMP13, and ADAMTS5) in chondrocytes. Ectopic expression of ZIP8 in mouse cartilage tissue caused OA cartilage destruction, whereas Zip8 knockout suppressed surgically induced OA pathogenesis, with concomitant modulation of Zn2+ influx and matrix-degrading enzymes. Furthermore, MTF1 was identified as an essential transcription factor in mediating Zn2+/ZIP8-induced catabolic factor expression, and genetic modulation of Mtf1 in mice altered OA pathogenesis. We propose that the zinc-ZIP8-MTF1 axis is an essential catabolic regulator of OA pathogenesis

A case of bilateral revision total knee arthroplasty using distal femoral allograft–prosthesis composite and femoral head allografting at the tibial site with a varus-valgus constrained prosthesis: ten-year follow up

Abstract Background We report the successful use of allograft–prosthesis composite (APC) and structural femoral head allografting in the bilateral reconstruction of large femoral and tibial uncontained defects during revision total knee arthroplasty (RTKA). Case presentation A 67-year-old female with degenerative arthritis underwent bilateral total knee arthroplasty (TKA) using the Press Fit Condylar (PFC) modular knee system at our clinic in March, 1996. At 8 years postoperatively, the patient presented with painful, bilateral varus knees, with swelling, limited passive range of motion (ROM), and severe instability. We treated to reconstruct both knee using a femoral head allograft at the tibial site, a structural distal femoral allograft at the femoral site, and a varus-valgus constrained (VVC) prosthesis with cement. At the 10-year follow up, we found no infection, graft failure, loosening of implants, in spite of using massive bilateral structural femoral head allografts in RTKA. Conclusion The use of APC enabled a stable and durable reconstruction in this uncommon presentation with large femoral bone deficiencies encountered during a RTKA

Clinical and radiological results of cruciate-retaining total knee arthroplasty with the NexGen®-CR system: comparison of patellar resurfacing versus retention with more than 14 years of follow-up

Abstract Background The purpose of this study is to analyze clinical and radiological outcomes of patients (with a minimum of 14 years of follow-up) who underwent cruciate-retaining (CR) total knee arthroplasty (TKA) using a NexGen®-CR, comparing a patellar resurfacing group with a patellar retention group. Methods From June 1996 to April 2002, 116 cases of TKA using a NexGen®-CR who had at least 14 years of follow-up were enrolled in this study. Among them, 68 cases had patellar resurfacing and 48 had patellar retention. The average follow-up period was 14.8 years (14.1–18.7). Clinical scores and range of motion (ROM) were evaluated preoperatively and at the last follow-up in all patients. The Hospital for Special Surgery (HSS) score, Knee Society Score (KSS), Western Ontario and MacMaster Universities Osteoarthritis (WOMAC) score, and a new patellar score were assessed. Radiological evaluations are done by analyzing the tibiofemoral angle, loosening, and a radiolucent line on the radiograph by American Knee Society Roentgen Graphic Evaluation. Results The average HSS score of both the patellar resurfacing group and retention group increased from 42.3 and 41.2 preoperatively to 90.2 and 90.8 at the last follow-up, respectively. The KSS, WOMAC score, patellar score, and knee joint ROM also improved significantly in both groups. However, there were no significant differences in clinical results between the two groups. On the radiological evaluation, the tibiofemoral angle in both groups had improved from varus 7.8° and 7.2° preoperative to valgus 4.9° and 4.8°, respectively. The average angles of α, β, γ, and δ were 94.1°, 90.4°, 3.2°, and 87.8° in the patellar resurfacing group and 94.4°, 89.8°, 3.3°, and 88.1° in the patellar retention group, respectively. A radiolucent line shown on radiograph was noted in a total of seven cases, three in the patellar resurfacing group and four in the patellar retention group. In the patellar resurfacing group, among the seven zones on the tibia radiograph, all cases were located at the medial side of tibia and two cases were in zone 1 and one case in zone 2, and in the patellar retention group, three cases were in zone 1 and 1 case was in zone 2, also located on the same side. Conclusions We achieved satisfactory clinical and radiological outcomes on long-term follow-up when performing TKAs with a NexGen®-CR. There was no significant difference in clinical or radiological results between the patellar resurfacing and retention groups in our study