Osteoarthritis (OA) is the most common form of arthritis worldwide. It is a major cause of disability in the adult population with its prevalence expected to increase dramatically over the next 20 years. Although current therapies can alleviate symptoms and improve function in early course of the disease, OA inevitably progresses to end-stage disease requiring total joint arthroplasty. Mesenchymal stromal cells (MSCs) have emerged as a candidate cell type with great potential for intra-articular (IA) repair therapy. However, there is still a considerable lack of knowledge concerning their behaviour, biology and therapeutic effects. To start addressing this, we explored the secretory profile of bone marrow derived MSCs in early and end-stage knee OA synovial fluid (SF). Subjects were recruited and categorised into early [Kellgren-Lawrence (KL) grade I and II, n=12] and end-stage (KL grade III and IV, n=11) knee OA groups. The SF proteome of early and end-stage OA was tested before and three days after the addition of bone marrow MSCs (16.5×10^3, single donor) using multiplex ELISA (64 cytokines) and mass spectrometry (302 proteins detected). Non parametric Wilcoxon-signed rank test for paired samples was used to compare the levels of proteins before and after addition of MSCs in early and end-stage knee OA SF. Significant differences were determined after multiple comparisons correction (FDR) with a p<0.05. Gender distribution and BMI were not statistically different between the two cohorts (p>0.05). However, patients in early knee OA cohort were significantly younger (44.7 years, SD=7.1) than patients in the end-stage cohort (58.6 years, SD=4.4; p<0.05). In both early and end-stage knee OA, MSCs increased the levels of VEGF-A (by 320.24 pg/mL), IL-6 (by 826.78 pg/mL) and IL-8 (by 128.85 pg/mL), factors involved in angiogenesis; CXCL1/2/3 (by 103.35 pg/mL), CCL2 (by 1187.27 pg/mL), CCL3 (by 15.82 pg/mL) and CCL7 (by 10.43 pg/mL), growth factors and chemokines. However, CXCL5 (by 48.61 pg/mL) levels increased only in early knee OA, whereas PDGF-AA (by 15.36 pg/mL) and CXCL12 (by 497.19 pg/mL) levels increased only in end-stage knee OA. This study demonstrates that bone marrow derived MSCs secrete angiogenic and chemotactic factors both in early and end-stage knee OA. More importantly, MSCs show a differential reaction between early and end-stage OA. Functional assays are required to further understand on how the therapeutic effect of MSCs is modulated when exposed to OA SF.
Mobile bearings in knee arthroplasty carry the theoretical advantage of lower wearing prostheses. However, dislocating mobile bearings can be a significant issue in mobile bearing knee replacement arthroplasty. Our aim is to report our design alterations to the insert to address bearing spinout. A total of 598 RBK mobile bearing total knee arthroplasties were performed by the senior author over a 10–year period. The standard bearing was subjected to three design changes to address spinout and increase flexion range. The first alteration involved a deeper dish with a higher anterior lip. Subsequently, a reduced footprint insert (RFI) was created. The final modification was a shaved off posterior rim to allow for greater flexion (high flex). An overall bearing dislocation rate of 1.0% (6 out of 595) was obtained. Of these 595 knees, 132 were of the initial insert design, 194 were deep-dished inserts, 71 inserts were RFI, and 198 were high flex. There were four (3%) dislocations with the initial insert design and two (1%) dislocations in the final implant version. In our series the dislocated bearings have in all but one required revision to higher constrained prostheses. The mechanism of dislocation is speculated to be instability in flexion, leading to posterior loading of the insert and spinning out of the bearing. Most of the bearing subluxations have been medial but one was observed intra operatively to be a lateral extrusion. With respect to the two dislocations in the final implant design, one dislocation was attributed to a technical error of under sizing the insert. At revision surgery he was also found to have a disrupted MCL, which was repaired. He has had no further issues after the insert was upsized . The cause of spin out in the second patient was speculated to be obesity and a diminished pre- operative range of movement. She required a revision to a higher constrained prosthesis. Insert spinout has a multifactorial aetiology. The occurrence of spinout can be minimised by a combination of good surgical technique, such as balanced flexion and extension gaps and design modifications to the insert as we have instituted.
