Tibial component fixation with a peri-apatite coating: evaluation by radiostereometric analysis in a canine total knee arthroplasty model.

Cementless fixation for the tibial component in total knee arthroplasty (TKA) remains problematic. Peri-Apatite (PA), a solution-deposited hydroxyapatite, is under investigation as an option for improving the fixation of cementless tibial components. In this study, radiostereometric analysis was used to document implant migration in 48 dogs that underwent TKA with cementless, PA-coated, or cemented tibial components. Migration at 12 weeks was similar in the 2 groups. At 12 months, there was greater migration in the PA-coated group, but the difference between the 2 groups was below the threshold considered clinically significant. In this canine TKA model, cementless fixation with PA performed less well than did cemented fixation, but not to a degree that would make a clinical difference in the short term.

12/15-Lipoxygenase signaling in the endoplasmic reticulum stress response.

Central obesity is associated with chronic inflammation, insulin resistance, ß-cell dysfunction, and endoplasmic reticulum (ER) stress. The 12/15-lipoxygenase enzyme (12/15-LO) promotes inflammation and insulin resistance in adipose and peripheral tissues. Given that obesity is associated with ER stress and 12/15-LO is expressed in adipose tissue, we determined whether 12/15-LO could mediate ER stress signals. Addition of 12/15-LO lipid products 12(S)-HETE and 12(S)-HPETE to differentiated 3T3-L1 adipocytes induced expression and activation of ER stress markers, including BiP, XBP-1, p-PERK, and p-IRE1α. The ER stress inducer, tunicamycin, upregulated ER stress markers in adipocytes with concomitant 12/15-LO activation. Addition of a 12/15-LO inhibitor, CDC, to tunicamycin-treated adipocytes attenuated the ER stress response. Furthermore, 12/15-LO-deficient adipocytes exhibited significantly decreased tunicamycin-induced ER stress. 12/15-LO action involves upregulation of interleukin-12 (IL-12) expression. Tunicamycin significantly upregulated IL-12p40 expression in adipocytes, and IL-12 addition increased ER stress gene expression; conversely, LSF, an IL-12 signaling inhibitor, and an IL-12p40-neutralizing antibody attenuated tunicamycin-induced ER stress. Isolated adipocytes and liver from 12/15-LO-deficient mice fed a high-fat diet revealed a decrease in spliced XBP-1 expression compared with wild-type C57BL/6 mice on a high-fat diet. Furthermore, pancreatic islets from 12/15-LO-deficient mice showed reduced high-fat diet-induced ER stress genes compared with wild-type mice. These data suggest that 12/15-LO activity participates in ER stress in adipocytes, pancreatic islets, and liver. Therefore, reduction of 12/15-LO activity or expression could provide a new therapeutic target to reduce ER stress and downstream inflammation linked to obesity.

Adipose tissue-specific deletion of 12/15-lipoxygenase protects mice from the consequences of a high-fat diet.

Type 2 diabetes is associated with obesity, insulin resistance, and inflammation in adipose tissue. 12/15-Lipoxygenase (12/15-LO) generates proinflammatory lipid mediators, which induce inflammation in adipose tissue. Therefore we investigated the role of 12/15-LO activity in mouse white adipose tissue in promoting obesity-induced local and systemic inflammatory consequences. We generated a mouse model for fat-specific deletion of 12/15-LO, aP2-Cre; 12/15-LO(loxP/loxP), which we call ad-12/15-LO mice, and placed wild-type controls and ad-12/15-LO mice on a high-fat diet for 16 weeks and examined obesity-induced inflammation and insulin resistance. High-fat diet-fed ad-12/15-LO exhibited improved fasting glucose levels and glucose metabolism, and epididymal adipose tissue from these mice exhibited reduced inflammation and macrophage infiltration compared to wild-type mice. Furthermore, fat-specific deletion of 12/15-LO led to decreased peripheral pancreatic islet inflammation with enlarged pancreatic islets when mice were fed the high-fat diet compared to wild-type mice. These results suggest an interesting crosstalk between 12/15-LO expression in adipose tissue and inflammation in pancreatic islets. Therefore, deletion of 12/15-LO in adipose tissue can offer local and systemic protection from obesity-induced consequences, and blocking 12/15-LO activity in adipose tissue may be a novel therapeutic target in the treatment of type 2 diabetes.

Cemented total knee replacement in 24 dogs: surgical technique, clinical results, and complications.

OBJECTIVE: To characterize the performance of cemented total knee replacement (TKR) in dogs. STUDY DESIGN: Preclinical research study. ANIMALS: Skeletally mature, male Hounds (25-30 kg; n=24) with no preexisting joint pathology. METHODS: Dogs had unilateral cemented TKR and were evaluated at 6, 12, 26, or 52 weeks (6 dogs/time point) by radiography, bone density analysis, visual gait assessment, and direct measurement of thigh circumference and stifle joint range of motion as indicators of functional recovery. At study end, the stability of the cemented tibial component was determined by destructive mechanical testing. RESULTS: Joint stability was excellent in 16 dogs (67%) and good in 8 dogs. None of the tibial components had evidence of migration or periprosthetic osteolysis whereas 1 femoral component was loose at 52 weeks. There was an early and significant decrease in tibial bone density, likely because of disuse of the operated limb. Dogs returned to full activity by 12 weeks. The tibial cement-bone interface maintained its strength over 52 weeks. CONCLUSIONS: Cement provides stable fixation of the tibial component in canine TKR. CLINICAL RELEVANCE: Cemented TKR yields adequate clinical function and stifle joint excursion in the dog. Clinical studies are needed to determine the long-term fate of cemented TKR implants, to assess the influence of implant design on implant fixation and wear, and to obtain objective functional data.

Tissue response to in situ polymerization of a new two-solution bone cement: evaluation in a sheep model.

A two-solution bone cement (2-SC) was evaluated in a non-load bearing sheep model that simulated insertion of a cemented total joint replacement. A commercial powder-liquid bone cement formulation (Palacos R) was used as the control. The systemic response to the two cements was determined by monitoring changes in arterial blood pressure (ABP) and serum concentrations of methyl methacrylate monomer at intervals after insertion of the cement. The short-term tissue response to the two cements was assessed by quantifying histomorphometric parameters of new bone formation at 2, 4, and 12 weeks postsurgery. Intraoperatively, injection and pressurization of bone cement were well tolerated, with no significant changes in ABP in either group and no detectable circulating monomer in any animal. Several interesting trends were identified in the histomorphometry data. In the trabecular specimens, new bone formation immediately adjacent to the cement mantle was apparently suppressed in the first 2 weeks postsurgery, increased dramatically at 4 weeks, and then returned to baseline values by 12 weeks. This pattern was seen with both Palacos and 2-SC. In the cortical specimens, new bone formation was reduced on the endosteal surface when compared with the periosteal surface, with this effect being more noticeable at 2 and 4 weeks than at 12 weeks. There were no significant histopathological findings in either the bone or the draining lymph nodes. These data indicate that the biological response to 2-SC is substantially equivalent to that of Palacos R. Additional testing in a functional, load-bearing animal model is now recommended to more fully characterize the long-term biological response to 2-SC and to determine the mechanical performance of this new cement in vivo.