Comparative bone anatomy of commonly used laboratory animals: implications for drug discovery.

To accommodate functional demands, the composition and organization of the skeleton differ among species. Microcomputed tomography has improved our ability markedly to assess structural parameters of cortical and cancellous bone. The current study describes differences in cortical and cancellous bone structure, bone mineral density, and morphology (geometry) at the proximal femur, proximal femoral diaphysis, lumbar vertebrae, and mandible in mice, rats, rabbits, dogs, and nonhuman primates.

Digigait quantitation of gait dynamics in rat rheumatoid arthritis model.

Introduction: Rheumatoid arthritis (RA) is characterized by joint pain, allodynia and hyperalgesia. The rat carrageenan model utilizes inflammation-associated pain following injection of the knee joint to model RA. Traditional assessment of pain in these models utilizes behavioral scoring or manual measurements, methods that are labor intensive and prone to subjective interpretation.

Bone parameters are improved with intermittent dosing of vitamin D3 and calcitonin.

Intermittent combination of an anabolic agent to promote bone formation and an antiresorptive agent that would prevent further bone loss is a theoretically attractive approach for restoring bone mass. We tested the potential of intermittently dosed calcitriol and calcitonin (CT) to restore bone properties in ovariectomized (Ovx) rats. Rats had Ovx or sham surgery at 8 weeks old and 4 weeks later were assigned to experimental groups: (1) sham vehicle, (2) Ovx vehicle, (3) Ovx + parathyroid hormone (PTH, 40 microg/kg), and (4) Ovx + calcitriol (2 microg/kg) + CT (2 microg/kg).

Age-related changes in marmoset trabecular and cortical bone and response to alendronate therapy resemble human bone physiology and architecture.

In older humans, bone elongation ceases, periosteal expansion continues, and bone remodeling remains a dominant metabolic process. An appropriate animal model of type I and type II osteoporosis would be a species with sealed growth plates and persistence of bone remodeling. The rat is commonly used as a primary model, but due to delayed epiphyseal closure with continuous modeling and lack of Haversian remodeling, Food and Drug Administration guidelines recommend assessment of bone quality in an additional, non rodent, remodeling species.

Quantitative trait loci for femoral size and shape in a genetically heterogeneous mouse population.

Unlabelled: The aim of this study was to examine the genetic effects on cortical bone geometry. Genotypes from 487 mice were compared with geometric traits obtained from microCT. We found 14 genetic markers that associate with geometric traits, showing the complexity of genetic control over bone geometry.

Bone morphogenetic protein-transduced human fibroblasts convert to osteoblasts and form bone in vivo.

Experimental cell or ex vivo gene therapy for localized bone formation typically uses osteoprogenitor cells propagated from periosteum or bone marrow. Both require bone or marrow biopsies to obtain cells. We have demonstrated that implantation of gingival or dermal fibroblasts transduced with BMP ex vivo, using a recombinant adenovirus (AdCMVBMP) attached to porous biodegradable scaffolds, form bone in vivo.

Mechanical stimulation induces pp125(FAK) and pp60(src) activity in an in vivo model of trabecular bone formation.

Utilizing an in vivo model of trabecular bone formation, we demonstrated the temporal and spatial activation of pp125(FAK) in response to specific mechanical load stimuli. Bone chambers equipped with hydraulic actuators were aseptically inserted into each proximal tibial metaphysis of adult, male dogs under general anesthesia. The load stimulus consisted of a trapezoidal waveform, with a maximum compressive load of 17.

An in vivo model for investigations of mechanical signal transduction in trabecular bone.

The premise that bone cells are able to perceive and respond to mechanical forces is well accepted. This article describes the use of an in vivo hydraulic bone chamber for investigations of mechanical signal transduction. The servohydraulic loading mechanism was activated to apply a controlled compressive load to the woven trabecular bone that formed in one chamber, while the contralateral chamber served as an unloaded control.

Perspectives on tissue engineering of bone.

The normal repair and regeneration of bone occurs through an ordered and regulated sequence of cellular events. Successful replacement of bone through tissue engineering likely will be dependent on the recapitulation of this cascade of events. This report presents some of the principles to be considered in the design of engineered bone constructs.

Molecular lysis of synovial lining cells by in vivo herpes simplex virus-thymidine kinase gene transfer.

Herpes simples virus thymidine kinase (HSV-TK) expression plasmid DNA was injected into the joint space of rabbits with antigen-induced arthritis (AIA). Purified plasmid DNA was able to mediate transfection of synovial lining cells and transient overexpression of HSV-TK in the context of active synovial inflammation. The pharmacodynamic distribution of intraarticular expression plasmid DNA was confined to the joint space.

Oxytetracycline-induced nephrotoxicosis in dogs after intravenous administration for experimental bone labeling.

Tetracyclines have been used as in vivo indicators of new bone formation because they form complexes with mineral at bone-forming surfaces. Four of 12 dogs in a bone-labeling study developed clinical signs of renal disease (vomiting, diarrhea, dehydration, and azotemia) within 1 to 2 days of receiving oxytetracycline at a bone-labeling dose of 25 mg/kg of body weight, once daily for 2 consecutive days. To delineate the relationship between oxytetracycline administration and renal damage, six dogs were given the bone-labeling dose intravenously and were subsequently evaluated by determination of clinical signs, serum biochemical analysis, urinalysis, and histologic examination (experiment 1).

Development and use of an animal model for investigations on rotator cuff disease.

Although both intrinsic and extrinsic factors have been implicated in the cause of rotator cuff disease, previous studies have not been designed to test hypotheses of this disease, partly because of the lack of an appropriate animal model. Thirty-three animals were evaluated according to a 34 item checklist of criteria to determine their appropriateness as an animal model for investigations on the rotator cuff. Only the rat shoulder satisfactorily fulfilled all criteria, with a prominent supraspinatus tendon passing under an enclosed arch.