The ferret as a small animal model with BMU-based remodelling for skeletal research

Mackey, Melissa; Stevens, M.L.; Ebert, D.C.; Tressler, D.L.; Combs, K.S.; Lowry, Catherine; Smith, Paul N.; McOsker, J.E.

doi:10.1016/8756-3282(95)00330-g

Cited by 21 publications

(12 citation statements)

References 5 publications

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“…However, the effect of ovariectomy on bone mass and the response to treatment might differ in these different models. For instance, the ferret model exhibits changes in bone remodeling and bone loss after ovariectomy [135,136]. Haversian bone remodeling is also observed.…”

Section: Specific Considerationmentioning

confidence: 95%

Importance of Preclinical Studies in the Development of Drugs for Treatment of Osteoporosis: A Review Related to the 1998 WHO Guidelines

Bonjour

Ammann

Rizzoli

1999

Osteoporosis International

100

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Osteoporosis, which is defined as a disease characterized by low bone mass and microarchitectural deterioration of bone tissue leading to enhanced bone fragility and a consequent increase in fracture risk, is a major health issue worldwide. Among the various strategies to prevent and cure this devastating ailment, an important objective is the development of new efficacious and safe drugs. This situation prompted the World Health Organization (WHO) to provide a comprehensive statement of guiding principles for the design, implementation and interpretation of both preclinical testing and clinical trials in osteoporosis. These guidelines, which are now available, underline the crucial importance of the preclinical evaluation, particularly for assessing the effect of an intervention on bone strength. This concept is heightened by the lack of a validated technique for noninvasively evaluating bone strength in humans and the multiple difficulties and heavy burden inherent in the evaluation of fracture rate in clinical trials. The WHO guidelines emphasize that a comprehensive and adequate preclinical program is expected to provide key information on the relationship between bone mass and strength and thus attenuate the burden of clinical studies. The present report provides a review of experimental evidence in support of the preclinical program as proposed in the WHO guidelines. This program is based on the recent development and refinement of animal models of osteoporosis that mimic the human condition according to the conceptual definition of the disease. Many preclinical studies carried out in appropriate animal models with agents that exert either antiresorbing or anabolic effects on bone indicate that they have been highly predictive of the drug action in humans in terms of both bone mass and remodeling, as well as of bone strength whenever fracture rate has been documented in clinical trials. Based on this evidence the WHO guidelines propose strategies according to which the results of preclinical evaluation will determine the end-points required in the different phases of the clinical development of the drug. Such a distribution of task assignment between preclinical and clinical programs should optimize the progress of research available to patients already suffering from or at risk of osteoporosis.

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Section: Specific Considerationmentioning

confidence: 95%

Importance of Preclinical Studies in the Development of Drugs for Treatment of Osteoporosis: A Review Related to the 1998 WHO Guidelines

Bonjour

Ammann

Rizzoli

1999

Osteoporosis International

100

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“…Male ferrets (Mustela putorius furo, Marshall Farms, North Rose, NY) were killed by an overdose of chloroform, and tissues were prepared as previously described [12,13]. Ferret tissues were used in this study because of the increased similarity of ferret proteins and physiological functions to the human relative to rodents [14][15][16].…”

Section: Tissue and Cell Preparationmentioning

confidence: 99%

The pro‐apoptotic protein Par‐4 facilitates vascular contractility by cytoskeletal targeting of ZIPK

Vetterkind¹,

Morgan²

2009

J Cellular Molecular Medi

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Par-4 (prostate apoptosis response 4) is a pro-apoptotic protein and tumour suppressor that was originally identified as a gene product up-regulated during apoptosis in prostate cancer cells. Here, we show, for the first time, that Par-4 is expressed and co-localizes with the actin filament bundles in vascular smooth muscle. Furthermore, we demonstrate that targeting of ZIPK to the actin filaments, as observed upon PGF-2α stimulation, is inhibited by the presence of a cell permeant Par-4 decoy peptide. The same decoy peptide also significantly inhibits PGF-2α induced contractions of smooth muscle tissue. Moreover, knockdown of Par-4 using antisense morpholino nucleotides results in significantly reduced contractility, and myosin light chain and myosin phosphatase target subunit phosphorylation. These results indicate that Par-4 facilitates contraction by targeting ZIPK to the vicinity of its substrates, myosin light chain and MYPT, which are located on the actin filaments. These results identify Par-4 as a novel regulator of myosin light chain phosphorylation in differentiated, contractile vascular smooth muscle.

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“…Like the rat, the OVX ferret exhibits bone loss in the proximal tibia (Mackey et al, 1995). They are easy to house, small in size and are a seasonally polyestrus.…”

Section: Ferretsmentioning

confidence: 99%

Animal models of osteoporosis - necessity and limitations

2001

eCM

243

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There is a great need to further characterise the available animal models for postmenopausal osteoporosis, for the understanding of the pathogenesis of the disease, investigation of new therapies (e.g. selective estrogen receptor modulators (SERMs)) and evaluation of prosthetic devices in osteoporotic bone. Animal models that have been used in the past include non-human primates, dogs, cats, rodents, rabbits, guinea pigs and minipigs, all of which have advantages and disadvantages. Sheep are a promising model for various reasons: they are docile, easy to handle and house, relatively inexpensive, available in large numbers, spontaneously ovulate, and the sheep's bones are large enough to evaluate orthopaedic implants. Most animal models have used females and osteoporosis in the male has been largely ignored. Recently, interest in development of appropriate prosthetic devices which would stimulate osseointegration into osteoporotic, appendicular, axial and mandibular bone has intensified. Augmentation of osteopenic lumbar vertebrae with bioactive ceramics (vertebroplasty) is another area that will require testing in the appropriate animal model. Using experimental animal models for the study of these different facets of osteoporosis minimizes some of the difficulties associated with studying the disease in humans, namely time and behavioral variability among test subjects. New experimental drug therapies and orthopaedic implants can potentially be tested on large numbers of animals subjected to a level of experimental control impossible in human clinical research.

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The ferret as a small animal model with BMU-based remodelling for skeletal research

Cited by 21 publications

References 5 publications

Importance of Preclinical Studies in the Development of Drugs for Treatment of Osteoporosis: A Review Related to the 1998 WHO Guidelines

Importance of Preclinical Studies in the Development of Drugs for Treatment of Osteoporosis: A Review Related to the 1998 WHO Guidelines

The pro‐apoptotic protein Par‐4 facilitates vascular contractility by cytoskeletal targeting of ZIPK

Animal models of osteoporosis - necessity and limitations

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