Are skeletally mature female rats a suitable model to study osteoporosis?

Netto, Claudia Cardoso; Vieira, Vivian Cristine Correia; Marinheiro, Lizanka Paola Figueiredo; Agellon, Sherry; Weiler, Hope A.; Maróstica, Mário Roberto

doi:10.1590/s0004-27302012000400007

Cited by 8 publications

(10 citation statements)

References 24 publications

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“…Serum osteoprotegerin (OPG) was determined by enzyme linked immunosorbent assay (ELISA) technique using R&D Elisa (SorinBiomedica, Eti-System, Denlay Instruments Ltd, England) kit as described by O'Brien et al (2001). Serum osteocalcin was also measured with osteocalcin (OC) rat ELISA system (Rat Bone Panel3 Millipore, MA, USA) (Netto et al 2012). Serum receptor activator of nuclear factor kappa B ligand (RANKL) levels were determined by enzyme linked immunosorbent assay (ELISA) technique using R&D ElIZA (SorinBiomedica, Eti-System, Denlay Instruments Ltd, England) kit as described by Teng et al (2000).…”

Section: Preparation Of Serummentioning

confidence: 99%

A comparative study between the effect of 17-β estradiol and angiotensin converting enzyme inhibitor on osteoporosis in ovariectomized rats

Alaam

Hussien²

2016

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Osteoprotegerin (OPG) and receptor activator of nuclear factor-kappa B ligand (RANKL) have been revealed in the pathogenesis of primary osteoporosis and other metabolic bone diseases. This study was designed to assess the effect of 17-β estradiol (E2) treatment and angiotensin converting enzyme inhibitor (ACEI), captopril, on osteoporosis induced by ovariectomy in rats and discussing the role of OPG/RANKL ratio in their action. Thirty two adult female rats were divided into four equal groups. Group I: control group, Group II: ovariectomized (OVX) non treated group, Group III: OVX rats treated with E2, Group IV: OVX rats treated with captopril. OVX rats showed a significant decrease in serum Ca2+ and OPG levels with significant increase in serum RANKL, osteocalcin, alkaline phosphatase activity and urinary hydroxyproline levels. Treatment with captopril as well as E2 led to a significant improvement in bone markers levels with a significant increase in OPG/RANKL ratio. Image analysis technique revealed that there was a significant improvement in cortical bone thickness (CBT) and mean trabecular bone density (TBD) in OVX rats treated with either E2 or ACEI. So, we can conclude that the protective effect of E2 and ACEI on osteoporosis may be mediated by influencing OPG/RANKL signaling.

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Section: Preparation Of Serummentioning

confidence: 99%

A comparative study between the effect of 17-β estradiol and angiotensin converting enzyme inhibitor on osteoporosis in ovariectomized rats

Alaam

Hussien²

2016

gpb

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“…Although young rats of 8–10 weeks are often used in orthopedic studies, we limited our study to 24 w and older. The rationale being that while female Wistar rats are sexually mature at 10 w old, they only reach skeletal maturity at 20 weeks . At younger age rapid growth is a highly confounding factor, therefore we cannot extrapolate our findings to non‐skeletally mature rats.…”

Section: Discussionmentioning

confidence: 94%

“…For practical reasons such as cost, time and supply or for comparability with previous reports, sexually mature rodents (8–12 weeks for mice, 5–10 weeks for rats) are used most of the time when age is not the primary focus . But skeletal maturity is reached later than sexual maturity . This lack of study‐adapted choice of animals’ age might negatively impact research outcomes, since such young animals are still experiencing physiological changes …”

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confidence: 99%

“…4 But skeletal maturity is reached later than sexual maturity. 18 This lack of study-adapted choice of animals' age might negatively impact research outcomes, since such young animals are still experiencing physiological changes. 19 Here, the aim of the study was to characterize the effects of age on the dynamics of implant fixation in a longitudinal rat model; and to compare it with the effect of osteoporosis.…”

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confidence: 99%

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Relative effects of age on implant integration in a rat model: A longitudinal in vivo microct study

Freitag

Günther

Eberli

et al. 2019

Journal Orthopaedic Research

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The effect of age on implant fixation in bone is not always considered during the design of preclinical models. The decision on animal's age is often related to practical or historical reasons, which ultimately may affect the reproducibility of results. This study aimed to quantify the effect of age by monitoring the fixation of contrast‐enhanced PEEK screws in rats, hypothesizing that the kinetics of fixation is impaired in older animals but that age effects are less severe than osteoporotic effects. The time course of implant fixation was investigated in healthy rats at 24, 40, and 60 weeks of age; and in ovariectomized rats. Implant fixation was monitored using in‐vivo microCT and dynamic histomorphometry during 1 month. The rats were euthanized 28 days post screw insertion. The data was analyzed both in absolute value and after normalization to baseline bone mass. In absolute terms, greater age had a detrimental effect on bone implant contact, bone fraction, implant stiffness, and bone remodeling but less than ovariectomy. Interestingly, once data was normalized to baseline bone mass this effect disappeared, suggesting that the physiologic response to implant placement was not affected by age. In conclusion, implant fixation kinetics is less affected by age than by baseline bone mass in this rat model. Animals of different ages can therefore be compared but data must be construed relatively to baseline bone mass and not in absolute terms. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 9999:1–12, 2018.

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“…44,45,46 Beneficial effects may be further increased through the delivery of RNAi effectors against RANKL to T-cells, in particular Th17 cells. Also, decreasing the levels of IL-17 may support the recovery of osteoporosis effects.…”

Section: Discussionmentioning

confidence: 99%

In Vivo siRNA Delivery Using JC Virus-like Particles Decreases the Expression of RANKL in Rats

Hoffmann

Böker

Schneider

et al. 2016

Molecular Therapy - Nucleic Acids

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Bone remodeling requires a precise balance between formation and resorption. This complex process involves numerous factors that orchestrate a multitude of biochemical events. Among these factors are hormones, growth factors, vitamins, cytokines, and, most notably, osteoprotegerin (OPG) and the receptor activator for nuclear factor-kappaB ligand (RANKL). Inflammatory cytokines play a major role in shifting the RANKL/OPG balance toward excessive RANKL, resulting in osteoclastogenesis, which in turn initiates bone resorption, which is frequently associated with osteoporosis. Rebalancing RANKL/OPG levels may be achieved through either upregulation of OPG or through transient silencing of RANKL by means of RNA interference. Here, we describe the utilization of a viral capsid-based delivery system for in vivo and in vitro RNAi using synthetic small interfering RNA (siRNA) molecules in rat osteoblasts. Polyoma JC virus-derived virus-like particles are capable of delivering siRNAs to target RANKL in osteoblast cells both in vitro and in a rat in vivo system. Expression levels were monitored using quantitative real-time polymerase reaction and enzyme-linked immunosorbent assay after single and repeated injections over a 14-day period. Our data indicate that this is an efficient and safe route for in vivo delivery of gene modulatory tools to study important molecular factors in a rat osteoporosis model.

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Are skeletally mature female rats a suitable model to study osteoporosis?

Cited by 8 publications

References 24 publications

A comparative study between the effect of 17-β estradiol and angiotensin converting enzyme inhibitor on osteoporosis in ovariectomized rats

A comparative study between the effect of 17-β estradiol and angiotensin converting enzyme inhibitor on osteoporosis in ovariectomized rats

Relative effects of age on implant integration in a rat model: A longitudinal in vivo microct study

In Vivo siRNA Delivery Using JC Virus-like Particles Decreases the Expression of RANKL in Rats

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