Total knee arthroplasty (TKA) is a common orthopaedic procedure with over 1,500 done in 2016 in Ireland alone. 96% of all TKAs are due to pain in the knee associated with osteoarthritis. According to the UK National Joint Registry (NJR), there is a 0.47%, 1.81%, 2.63% and 4.34% probability risk of undergoing a revision TKA within one, three, five and ten years respectively post-index surgery. A variety of reasons for failure of TKA have been described in the literature including infection, aseptic loosening, pain, instability, implant wear, mal-alignment, osteolysis, dislocation, peri-prosthetic fracture and implant fracture. The NexGen Posterior Stabilised Fixed has NJR revision rates of 0.44%, 1.61% and 2.54% at years one, three and five respectively. A retrospective review was carried out of 350 NexGen TKAs that were performed directly by, or under the supervision of, a fellowship trained arthroplasty surgeon in a dedicated orthopaedic hospital between April 2013 and December 2015. 26 (7.4%) of these were revised as of 31 December 2017. Three were for septic arthritis with the remaining 23 (6.6%) for aseptic loosening. Patients typically started to experience symptoms of medial tibial pain with supra-patellar swelling from a combination of effusion and
Introduction. Osteoarthritis (OA) of the knee, a prevalently degenerative joint disorder provoked by articular cartilage loss, accounts for the leading cause of total knee arthroplasty. Autophagy is an indispensable intracellular event that maintains chondrocyte survival and metabolism. MicroRNAs are non-coding small RNAs participating in tissue morphogenesis, remodeling, and homeostasis. This study was undertaken to investigate the effect of microRNA-128 (miR-128) knockdown on the development of OA knees. Materials/Methods. Knee joints in rats were subjected to anterior cruciate ligament transection (ACLT) for inducing OA. Articular cartilage, synovium, and subchondral bone microarchitecture were assessed by OARSI scoring system, histomorphometry, and μCT imaging. Chondrocyte autophagy in terms of the expression of autophagic markers Atg4, Atg12, microtubule-associated protein 1 light chain 3 (LC3), and autophagosome formation was verified. Expression of microRNA, mRNA and signaling transduction were quantified with in situ hybridization, RT- quantitative PCR, and immunoblotting. Results. Chondrocytes in the affected knees showed weak expression of autophagic markers Atg4, Atg12, and LC3-II abundances in conjunction with significant increases in OARSI scores and a 2.5-fold elevation in miR-128 expression. The gain of miR-128 signaling in intact joints through intra-articular injection of miR-128 precursor resulted in 1.8–2.1-fold elevations in serum cartilage breakdown products CTX-II and COMP concentrations. miR-128 overexpression caused the joints to show evident chondrocyte apoptosis as evidenced by TUNEL staining concomitant with severe cartilage damage. Of note, antisense oligonucleotide knockdown of miR-128 (miR-128-AS) enabled the affected knee joints to show minor responses to the ACLT escalation of autophagy dysfunction in chondrocytes, cartilage breakdown histopathology, and OARSI scores. Administration with miR-128-AS also attenuated the ACLT-induced
