Protein biomarkers in serum and urine for determining presence or absence of hip dysplasia in a canine model.

This study compares serum and urine concentrations of relevant protein biomarkers among adult dogs with or without radiographic canine hip dysplasia (CHD). Adult (≥2 years of age), client-owned dogs (n = 74) radiographically categorized as having at least "good" hips (n = 49) or having "mild," "moderate," or "severe" hip dysplasia (n = 25) by the Orthopedic Foundation for Animals (OFA). Urine and serum samples were obtained from each dog at a single time-point and processed and analyzed for relevant protein biomarkers. Urinary concentrations of CTX-II (p < 0.001) and TIMP-1 (p = 0.002) were significantly lower in dogs with CHD compared to dogs with no CHD. ROC curve analyses were successful in establishing a panel of four biomarkers (urinary CTX-I and II, serum MMP-9, and serum PIICP) with high discriminatory capability for the presence or absence of hip dysplasia in adult dogs (AUC = 0.89). Urine and serum biomarkers can distinguish adult dogs with radiographic CHD from those with no CHD with a sensitivity of 0.95 and specificity of 0.77 using ROC analysis with AUC 0.89. Clinical Significance: This finding suggests that this simple, minimally invasive diagnostic technique has potential for discriminating dysplastic dogs from dogs with normal hips, with possible translational application to humans based on similar etiopathogenesis. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 9999:1-5, 2019.

Assessment of Reamer Irrigator Aspirator System (RIA) filtrate for its osteoinductive potential in a validated animal model.

PURPOSE: Previous studies indicate that Reamer Irrigator Aspirator (RIA) filtrate contains proteins that have the potential to stimulate bone healing. This study aimed to determine the osteoinductive capabilities of RIA filtrate in a validated in vivo model. METHODS: With Institutional Review Board approval, RIA filtrates from 9 patients were collected. The filtrate was processed to remove cells and inorganic particles. A portion of each sample was set aside for protein analysis while the remainder was lyophilized and prepared for implantation. With Animal Care and Use Committee approval, athymic mice (n = 16; 32 hind limbs) were randomly assigned to 1 of 4 groups (n = 8 limbs per group) for percutaneous gastrocnemius muscle injection of demineralized bone matrix (DBM) (10 mg), lyophilized RIA powder (10 mg), RIA liquid (10 mg of lyophilized RIA powder in 100ul phosphate buffered saline (PBS)), or DBM (10 mg) + RIA liquid (10 mg in 100ul PBS). Radiographs were obtained 2, 4, and 8 weeks after injection. At 8 weeks, mice were sacrificed and the entire gastrocnemius muscle from each hind limb was collected and processed for histologic examination. Histological sections and radiographs were assessed for ossification/calcification. Data were compared for statistically significant (p < 0.05) differences among groups and strong (R > 0.7) correlations between outcome measures. RESULTS: The protein composition of RIA filtrates was consistent among patients and matched previous data. For all groups, radiographic scores were significantly (p < 0.014) higher (more calcification/ossification) at 8 weeks compared to 2 weeks. Radiographic scores for the DBM and DBM + RIA liquid groups were significantly higher than RIA liquid and RIA powder at 4 weeks and 8 weeks (p < 0.019 and p < 0.049, respectively). Histologic scores were significantly (p = 0.004) higher in the DBM + RIA liquid group compared to the RIA liquid group at 8 weeks. Histologic scores showed strong correlations (r > 0.77) to radiographic scores for all groups. CONCLUSION: RIA filtrate liquid and powder were osteoinductive in vivo with new bone formation being most abundant using a combination of DBM and RIA filtrate in this validated animal model. RIA filtrate has potential for clinical use in augmenting bone healing treatments.

Differential susceptibility to colorectal cancer due to naturally occurring gut microbiota.

Recent studies investigating the human microbiome have identified particular bacterial species that correlate with the presence of colorectal cancer. To evaluate the role of qualitatively different but naturally occurring gut microbiota and the relationship with colorectal cancer development, genetically identical embryos from the Polyposis in Rat Colon (Pirc) rat model of colorectal cancer were transferred into recipients of three different genetic backgrounds (F344/NHsd, LEW/SsNHsd, and Crl:SD). Tumor development in the pups was tracked longitudinally via colonoscopy, and end-stage tumor burden was determined. To confirm vertical transmission and identify associations between the gut microbiota and disease phenotype, the fecal microbiota was characterized in recipient dams 24 hours pre-partum, and in Pirc rat offspring prior to and during disease progression. Our data show that the gut microbiota varies between rat strains, with LEW/SsNHsd having a greater relative abundance of the bacteria Prevotella copri. The mature gut microbiota of pups resembled the profile of their dams, indicating that the dam is the primary determinant of the developing microbiota. Both male and female F344-Pirc rats harboring the Lewis microbiota had decreased tumor burden relative to genetically identical rats harboring F344 or SD microbiota. Significant negative correlations were detected between tumor burden and the relative abundance of specific taxa from samples taken at weaning and shortly thereafter, prior to observable adenoma development. Notably, this naturally occurring variation in the gut microbiota is associated with a significant difference in severity of colorectal cancer, and the abundance of certain taxa is associated with decreased tumor burden.