The objective of the present study was to determine if naturally occurring osteoarthritis of the knee joints that is similar to the condition in humans develops in cynomolgus macaques. Knee joints from 58 young adult (mean age, 7.4 years) female cynomolgus macaques were studied with x-ray densitometry, high-detail radiography, and histology. The animals studied were subjects in a triad designed to examine the effects of the administration of sex steroids on atherosclerosis; except for a control group, the monkeys had been either ovariectomized or treated with sex steroids for 2 years. Therefore, the data were analyzed to determine if these treatments, both of which can influence bone density, affected the severity of osteoarthritis. There was a high prevalence of osteoarthritic lesions, morphologically similar to those seen in humans. Bone changes were more common and severe than cartilage changes and morphologically appeared to precede the cartilage changes. Treatment with testosterone resulted in increased body weight, body mass index, and bone mineral content in the femur and tibia but did not affect the severity of osteoarthritis. These data indicate that naturally occurring osteoarthritis developed in the knee joints of cynomolgus macaques; these animals may be a useful model for the study of osteoarthritis in humans.

. Tubular cell-enriched subpopulation of primary renal cells improves survival and augments kidney function in rodent model of chronic kidney disease. Am J Physiol Renal Physiol 299: F1026 -F1039, 2010. First published September 8, 2010 doi:10.1152/ajprenal.00221.2010.-Established chronic kidney disease (CKD) may be identified by severely impaired renal filtration that ultimately leads to the need for dialysis or kidney transplant. Dialysis addresses only some of the sequelae of CKD, and a significant gap persists between patients needing transplant and available organs, providing impetus for development of new CKD treatment modalities. Some postulate that CKD develops from a progressive imbalance between tissue damage and the kidney's intrinsic repair and regeneration processes. In this study we evaluated the effect of kidney cells, delivered orthotopically by intraparenchymal injection to rodents 4 -7 wk after CKD was established by two-step 5/6 renal mass reduction (NX), on the regeneration of kidney function and architecture as assessed by physiological, tissue, and molecular markers. A proof of concept for the model, cell delivery, and systemic effect was demonstrated with a heterogeneous population of renal cells (UNFX) that contained cells from all major compartments of the kidney. Tubular cells are known contributors to kidney regeneration in situ following acute injury. Initially tested as a control, a tubular cellenriched subpopulation of UNFX (B2) surprisingly outperformed UNFX. Two independent studies (3 and 6 mo in duration) with B2 confirmed that B2 significantly extended survival and improved renal filtration (serum creatinine and blood urea nitrogen). The specificity of B2 effects was verified by direct comparison to cell-free vehicle controls and an equivalent dose of non-B2 cells. Quantitative histological evaluation of kidneys at 6 mo after treatment confirmed that B2 treatment reduced severity of kidney tissue pathology. Treatmentassociated reduction of transforming growth factor (TGF)-␤1, plasminogen activator inhibitor (PAI)-1, and fibronectin (FN) provided evidence that B2 cells attenuated canonical pathways of profibrotic extracellular matrix production. regeneration; stabilization CHRONIC KIDNEY DISEASE (CKD) affects more than 19 million people in the U.S. and frequently develops as a consequence of chronic obesity, diabetes, and/or hypertension (42). Patients in stage 4 -5 CKD receive dialysis and a complex drug regimen, and the number of kidneys available for transplant is vastly insufficient to meet the need (30). New treatments that delay or reduce dialysis dependence are needed to fill this void.Kidney tissue is composed of Ͼ20 specialized cell types structurally organized into morphologically and functionally distinct compartments that act in concert to filter blood, produce urine, and regulate endocrine function and acid-base and electrolyte balance. Cell-cell interactions are critical to kidney function and are at least partially dependent on spatial and architectural relations...

A cross-sectional study by age was designed to evaluate and describe the bone mineral content (BMC, g) and density (BMD, g/cm2) in a population of female cynomolgus macaques (Macaca fascicularis). Dual-energy X-ray absorptiometry was used to measure, in segments L2-L4 of the lumbar spine, the BMC (BMCs), BMD (BMDs), length, and total-body BMC(BMCTB) in 171 female monkeys ranging in age between 3.7 and 22.0 years. The animals were divided into three age groups: (1) young (< 6.5 years, n = 51); (2) adult (> 6.5 years and < 10.5 years, n = 63); and (3) mature (> 10.5 years, n = 57). Young animals had a significantly lower (P < 0.05) body weight and shorter trunk length than adult or mature animals. Young animals also had significantly less (P < 0.05) BMCS, BMDS, and BMCTB than adult or mature animals, and had significantly shorter (P < 0.01) lumbar spine vertebral segments than the other two groups. Longitudinally, 63 animals had repeated lumbar spine scans to examine changes over time. Young animals showed a positive and significant change (P < 0.05) in BMCs and BMDs through time, whereas these parameters did not change in adult animals, and mature animals had a trend towards bone loss through time. Densitometric results suggested that peak bone mass in the lumbar spine was achieved by 9 years of age. Radiographic and dental criteria were developed to identify animals that had reached peak bone mass, and the combined radiographic and dental scoring system reliably identified animals 9 years and older. Female cynomolgus macaques 9 years old or older are recommended for investigations of bone remodeling and associated conditions, such as osteoporosis.