Age-Linked Modification of the Effect of Estrogen on Joints and Cortical Bone of Female Mice

Silberberg, Martin; Silberberg, Ruth

doi:10.1159/000211772

Cited by 20 publications

(8 citation statements)

References 12 publications

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“…However, administration of estrogens to C57BL and C3H female mice also results in FOLs (Silberberg and Silberberg, 1970;Highman et al, 1981), but administration of DES to CF1 female mice again fails to cause FOLs (Johnson, 1987). The mice used in the current study were all derived from the C57BL/6 strain, and the occurrence of FOLs in all 3 genotypes, including the wild-type animals, indicates that both females and males of this strain are susceptible to this lesion.…”

Section: Discussionmentioning

confidence: 61%

Diethylstilbestrol (DES): Carcinogenic Potential in Xpa^−/−, Xpa^−/−/p53^+/−, and Wild-Type Mice During 9 Months’ Dietary Exposure

McAnulty¹,

Skydsgaard²

2005

Toxicol Pathol

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DES carcinogenicity has been investigated in 2 mouse knockout models, the Xpa homozygous knockout, and the combined Xpa homozygous and p53 heterozygous knockout. Wild-type (WT) mice were also included. Xpa mice received diets containing DES at concentrations of 0, 100, 300, and 1500 ppb for 39 weeks; Xpa/p53 and WT mice received diets containing 0 or 1500 ppb. There were 15 of each sex per group. Both Xpa and WT mice had a similar incidence of tumors at the high dosage of 1500 ppb, including pituitary adenomas in 4 WT mice and 7 Xpa mice, and single incidences of osteosarcoma (Xpa), T-cell lymphoma (WT and Xpa), and testicular interstitial cell adenoma (WT and Xpa). The incidence of tumors was higher in the Xpa/p53 mice at 1500 ppb, mainly attributable to 5 osteosarcomas in males and 2 in females, but also 4 pituitary adenomas, testicular interstitial cell adenomas in 4 males, and single incidences of cerebral glioma, phaeochromocytoma, and cervical fibrosarcoma. The incidence of osteosarcomas was related to the severity of fibro-osseous lesions in the bone marrow. It was concluded that for carcinogenicity screening, Xpa mice were no more sensitive than wild-type mice for compounds like DES, but the Xpa/p53 model showed an increased sensitivity.

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Section: Discussionmentioning

confidence: 61%

Diethylstilbestrol (DES): Carcinogenic Potential in Xpa^−/−, Xpa^−/−/p53^+/−, and Wild-Type Mice During 9 Months’ Dietary Exposure

McAnulty¹,

Skydsgaard²

2005

Toxicol Pathol

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“…It should be also emphasized that incidence and progress of degenerative osteoarthrosis in mice extremely vary with strain [8,9,14]. Further, some strains show a quite different incidence of the lesion with sex [5][6][7][8][9]14]. Thus, genetic predisposition in this disease can not be denied.…”

Section: Discussionmentioning

confidence: 99%

“…Degenerative osteoarthrosis known to occur in large or small synovial joints has been described widely for man and other animals including mice [1][2][3][4][5][6][7][8][9][10][11][12][13][14].…”

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confidence: 99%

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Degenerative Osteoarthrosis in Aged ICR Mice

Yamasaki

1986

Experimental Animals

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The tibia of 117 aged ICR mice was examined histologically to provide further information on degenerative osteoarthrosis.Incidence of the lesion became higher in the male older than 480 days of age and in the female older than 450 days. Main gross changes were roughening of the articular surface, narrowing or focal thickening of the articular cartilage, and osteophytes at the margins of the joint. Histology revealed loosening of the matrix, erosion, and marginal osteophytes in the articular cartilage, and sclerotic changes of the subchondral bone.

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“…There is evidence for an associated hormonal imbalance, based on a strong sexual dichotomy where females are almost exclusively affected. Also, when mice of both sexes are treated with estrogen, they developmore severe fibro-osseous lesions earlier than seen in the spontaneous disease (Highman et al, 1981; Sass and Montali 1980; Silberberg and Silberberg 1970). Fibro-osseous lesions in B6C3F1 mice are often accompanied by ovarian cysts and cystic endometrial hyperplasia and, thus, could be caused by estrogen-producing cysts (Sass and Montali 1980).…”

Section: Introductionmentioning

confidence: 99%

Genetic determinants of fibro-osseous lesions in aged inbred mice

Berndt

Ackert‐Bicknell

Silva

et al. 2016

Experimental and Molecular Pathology

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Fibro-osseous lesions in mice are progressive aging changes in which the bone marrow is replaced to various degrees by fibrovascular stroma and bony trabeculae in a wide variety of bones. The frequency and severity varied greatly among 28 different inbred mouse stains, predominantly affecting females, ranging from 0% for 10 strains to 100% for KK/HlJ and NZW/LacJ female mice. Few lesions were observed in male mice and for 23 of the strains, no lesions were observed in males for any of the cohorts. There were no significant correlations between strain-specific severities of fibro-osseous lesions and ovarian (r=0.11; P=0.57) or endometrial (r=0.03; P=0.89) cyst formation frequency or abnormalities in parathyroid glands. Frequency of fibro-osseous lesions was most strongly associated (P < 10−6) with genome variations on chromosome (Chr) 8 at 90.6 and 90.8 Mb (rs33108071, rs33500669; P = 5.0 · 10−10, 1.3 · 10−6), Chr 15 at 23.6 and 23.8 Mb (rs32087871, rs45770368; P = 7.3 · 10−7, 2.7 · 10−6), and Chr 19 at 33.2, 33.4, and 33.6 Mb (rs311004232, rs30524929, rs30448815; P=2.8 · 10−6, 2.8 · 10−6, 2.8 · 10−6) in genome-wide association studies (GWAS). The relatively large number of candidate genes identified in the GWAS analyses suggests that this may be an extremely complex polygenic disease. These results indicate that fibro-osseous lesions are surprisingly common in many inbred strains of laboratory mice as they age. While this presents little problem in most studies that utilize young animals, it may complicate aging studies, particularly those focused on bone.

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Age-Linked Modification of the Effect of Estrogen on Joints and Cortical Bone of Female Mice

Cited by 20 publications

References 12 publications

Diethylstilbestrol (DES): Carcinogenic Potential in Xpa^−/−, Xpa^−/−/p53^+/−, and Wild-Type Mice During 9 Months’ Dietary Exposure

Diethylstilbestrol (DES): Carcinogenic Potential in Xpa^−/−, Xpa^−/−/p53^+/−, and Wild-Type Mice During 9 Months’ Dietary Exposure

Degenerative Osteoarthrosis in Aged ICR Mice

Genetic determinants of fibro-osseous lesions in aged inbred mice

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Age-Linked Modification of the Effect of Estrogen on Joints and Cortical Bone of Female Mice

Cited by 20 publications

References 12 publications

Diethylstilbestrol (DES): Carcinogenic Potential in Xpa−/−, Xpa−/−/p53+/−, and Wild-Type Mice During 9 Months’ Dietary Exposure

Diethylstilbestrol (DES): Carcinogenic Potential in Xpa−/−, Xpa−/−/p53+/−, and Wild-Type Mice During 9 Months’ Dietary Exposure

Degenerative Osteoarthrosis in Aged ICR Mice

Genetic determinants of fibro-osseous lesions in aged inbred mice

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Product

Resources

About

Diethylstilbestrol (DES): Carcinogenic Potential in Xpa^−/−, Xpa^−/−/p53^+/−, and Wild-Type Mice During 9 Months’ Dietary Exposure

Diethylstilbestrol (DES): Carcinogenic Potential in Xpa^−/−, Xpa^−/−/p53^+/−, and Wild-Type Mice During 9 Months’ Dietary Exposure