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It is unknown whether activity-based physical therapy (ABPT) modalities that mobilize the paralyzed limbs improve bone integrity at the highly fracture-prone epiphyseal regions of the distal femur and proximal tibia following severe spinal cord injury (SCI). In this study, 4-mo-old skeletally mature littermate-matched male Sprague-Dawley rats received either SHAM surgery or severe contusion SCI. At 1 wk postsurgery, SCI rats were stratified to undergo no-ABPT, two 20-min bouts/day of quadrupedal bodyweight-supported treadmill training (qBWSTT), or hindlimb passive isokinetic bicycle (cycle) training, 5 days/wk for another 3 wk. We assessed locomotor recovery and plantar flexor muscle mass, tracked cancellous and cortical bone microstructure at the distal femoral and proximal tibial epiphyses using in vivo microcomputed tomography (microCT), and evaluated bone turnover at the tibial epiphysis with histomorphometry. All SCI animals displayed persistent hindlimb paralysis and pervasive muscle atrophy. Over the initial 2 wk, which included 1 wk of no exercise and 1 wk of ABPT acclimation, a similar magnitude of bone loss developed in all SCI groups. Thereafter, cancellous bone loss and cortical bone decrements increased in the SCI no-ABPT group. qBWSTT attenuated this trabecular bone loss but did not prevent the ongoing cortical bone deficits. In comparison, twice-daily cycle training increased the number and activity of osteoblasts versus other SCI groups and restored all bone microstructural parameters to SHAM levels at both epiphyseal sites. These data indicate that a novel passive isokinetic cycle training regimen reversed cancellous and cortical bone deterioration at key epiphyseal sites after experimental SCI via osteoblast-mediated bone anabolic mechanisms, independent of locomotor recovery or increased muscle mass. NEW & NOTEWORTHY: This study was the first to assess how quadrupedal bodyweight-supported treadmill training or passive isokinetic bicycle (cycle) training impacts bone recovery at the distal femoral and proximal tibial epiphyses in a rat model of severe contusion spinal cord injury. Our results demonstrate that passive isokinetic cycle training completely restored cancellous and cortical bone microstructural parameters at these sites via osteoblast-mediated bone anabolic actions, independent of locomotor recovery or increased plantar flexor muscle mass. [ABSTRACT FROM AUTHOR]

The Wnt family of secreted glycoproteins had previously been shown to regulate diverse processes during early development. Wnt signaling also plays a key role in the homeostasis of adult tissues maintaining stem cell pluripotency and determining differentiating cell fate. The age-related decrease in Wnt signaling may contribute to increased muscle adiposity and diminished bone strength. In the current study, we investigated the long-term metabolic consequences of the upregulated Wnt/[beta]-catenin signaling in skeletal muscles of adult diet-induced obese (DIO) rats. To this end, we generated a recombinant adeno-associated virus (rAAV) vector encoding murine Wnt10b cDNA. The long-term expression of rAAV1-Wnt10b was tested after intramuscular injection in the female DIO rat. Animals fed high-fat diet and treated with rAAV1-Wnt10b showed a sustained reduction in body weight compared with controls, and expression of Wnt10b was accompanied by a reduction in hyperinsulinemia and triglyceride plasma levels as well as improved glucose homeostasis. Nuclear magnetic resonance methods revealed that ectopic expression of Wnt10b resulted in a decrease in both global and muscular fat deposits in DIO rats. The long-range effect of locally expressed Wnt10b was also manifested through the increased bone mineral density. The detailed analysis of molecular markers revealed fibroblast growth factor-4 and vascular endothelial growth factor as possible mediators of the systemic effect of Wnt10b transgene expression. Our data demonstrate that altering Wnt/[beta]-catenin signaling in the skeletal muscle of an adult animal invokes moderate responses with favorable metabolic profile, bringing the notion of alternative therapeutic modality in the treatment of obesity, diabetes, and osteoporosis. Wnt10b; gene therapy; obesity: diabetes

Marsh rice rats (Oryzomys palustris) fed a pelleted diet high in sucrose and casein have been used as a model for moderate to severe periodontitis. Here we characterize the prevalence, location, and histopathologic features of food-impaction lesions (FIL), a unique type of oral event, in rice rats fed standard pelleted rodent chow from weaning until 34 wk of age. Healthy female rats (n = 90; age, 4 wk) were weaned into groups (n = 10 to 24) and were euthanized at 4, 16, 22, 28, or 34 wk of age. At necropsy, high-resolution photographs of the 4 jaw quadrants were examined by 3 independent observers to determine the presence, number, and location of FIL. In addition, gross periodontitis was scored (scale, 0 to 4), and the hemimaxillar surface area containing FIL was measured. Serial sections of decalcified jaws were assessed histologically. The prevalence of FIL increased with age, and was 0% (baseline), 59.1%, 69.6%, 81.8% and 80.0% in rats at age 4, 16, 22, 28, and 34 wk, respectively. FIL were predominantly located (93.9%) in the maxillary palatal surfaces of the interproximal area between molars 2 and 3 and did not affect mandibular surfaces. The percentage of the hemimaxillar surface area occupied by FIL was 6.83%, 4.82%, 2.88%, and 6.52% in rats at age 16, 22, 28, and 34 wk, respectively. Histopathologic changes in FIL varied from localized gingivitis to larger, localized periodontitis-like lesions. These data indicate that FIL are common in rice rats fed standard rodent chow, are slight to mild in severity, and are localized to specific regions in the oral cavity, thus suggesting they may be a suitable model for local maxillary periodontitis when fed standard rodent chow.

Published reports of spontaneous neoplasia in marsh rice rats (Oryzomys palustris) are sparse. We report here a case of cutaneous epitheliotropic T-cell lymphoma in a 14-mo-old marsh rice rat that involved the ear pinnae, with dissemination to the liver and spleen. Histologically, the thickened ear pinnae showed diffuse infiltration of neoplastic lymphocytes into the epidermis, dermis, and adnexal skin structures, with Pautrier microaggregations present in the epidermis. In addition, neoplastic lymphocytes were observed infiltrating and disrupting the architecture of the liver and spleen. Neoplastic lymphocytes were strongly positive for the T-cell marker CD3 but were negative for the B-cell markers CD19 and CD20. These histologic and immunohistochemical features are consistent with an epitheliotropic T-cell lymphoma, as previously reported in other species, including humans. To our knowledge, this report represents the first published case of spontaneous cutaneous epitheliotropic T-cell lymphoma in a marsh rice rat.

Spinal cord injury (SCI) results in rapid and extensive sublesional bone loss. Sclerostin, an osteocyte-derived glycoprotein that negatively regulates intraskeletal Wnt signaling, is elevated after SCI and may represent a mechanism underlying this excessive bone loss. However, it remains unknown whether pharmacologic sclerostin inhibition ameliorates bone loss subsequent to SCI. Our primary purposes were to determine whether a sclerostin antibody (Scl-Ab) prevents hindlimb cancellous bone loss in a rodent SCI model and to compare the effects of a Scl-Ab to that of testosterone-enanthate (TE), an agent that we have previously shown prevents SCI-induced bone loss. Fifty-five (n = 11-19/group) skeletally mature male Sprague-Dawley rats were randomized to receive: (A) SHAM surgery (T8 laminectomy), (B) moderate-severe (250 kilodyne) SCI, (C) 250 kilodyne SCI + TE (7.0 mg/wk, im), or (D) 250 kilodyne SCI + Scl-Ab (25 mg/kg, twice weekly, sc) for 3 weeks. Twenty-one days post-injury, SCI animals exhibited reduced hindlimb cancellous bone volume at the proximal tibia (via μCT and histomorphometry) and distal femur (via μCT), characterized by reduced trabecular number and thickness. SCI also reduced trabecular connectivity and platelike trabecular structures, indicating diminished structural integrity of the remaining cancellous network, and produced deficits in cortical bone (femoral diaphysis) strength. Scl-Ab and TE both prevented SCI-induced cancellous bone loss, albeit via differing mechanisms. Specifically, Scl-Ab increased osteoblast surface and bone formation, indicating direct bone anabolic effects, whereas TE reduced osteoclast surface with minimal effect on bone formation, indicating antiresorptive effects. The deleterious microarchitectural alterations in the trabecular network were also prevented in SCI + Scl-Ab and SCI + TE animals, whereas only Scl-Ab completely prevented the reduction in cortical bone strength. Our findings provide the first evidence indicating that sclerostin inhibition represents a viable treatment to prevent SCI-induced cancellous and cortical bone deficits and provides preliminary rationale for future clinical trials focused on evaluating whether Scl-Ab prevents osteoporosis in the SCI population., (© 2014 American Society for Bone and Mineral Research.)

Rice rats (Oryzomys palustris) are a recognized animal model for studying periodontal disease and the photoperiodic regulation of reproduction. Here we share information regarding the breeding, husbandry, veterinary care, and hematologic findings about this animal species to facilitate its use in studies at other research institutions. Rice rats initially were quarantined and monitored for excluded pathogens by using microbiologic, parasitologic, and serologic methods with adult female Mus musculus and Rattus norvegicus sentinel animals. Breeders were paired in a monogamous, continuous-breeding system. Rats were housed in static filter-top cages, maintained on commercial chow under 14:10-h light:dark cycles at 68 to 79 °F (20.0 to 26.1 °C) and 30% to 70% humidity. Rice rats apparently adapt relatively well to standard laboratory conditions, despite their aggressive behavior toward conspecifics and humans. Our analysis of 97 litters revealed that dams gave birth to an average of 5.2 pups per dam and weaned 4.2 pups per dam. Several procedures and biologic reagents normally used in standard laboratory rodents (mice and rats) can be used with rice rats. In addition, we present hematologic and serum chemistry values that can be used as preliminary reference values for future studies involving rice rats.