Reproductive Hormones and Bone

Nicks, Kristy M.; Fowler, Tristan W.; Gaddy, Dana

doi:10.1007/s11914-010-0014-3

Cited by 45 publications

(28 citation statements)

References 52 publications

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“…Reproductive hormones fluctuations have a well-established role in osteoporosis. In early menopause, the acute phase of estrogens deficiency is associated with an increased bone loss [1]. However, clinical studies, have provided evidence that the etiology of this disease is more complex than just a question of estrogen withdrawal and that overall bone mass is influenced by many environmental, but also genetic factors [2].…”

Section: Introductionmentioning

confidence: 99%

Control of Bone Resorption by Semaphorin 4D Is Dependent on Ovarian Function

et al. 2011

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Osteoporosis is one of the most common bone pathologies, which are characterized by a decrease in bone mass. It is well established that bone mass, which results from a balanced bone formation and bone resorption, is regulated by many hormonal, environmental and genetic factors. Here we report that the immune semaphorin 4D (Sema4D) is a novel factor controlling bone resorption. Sema4D-deficient primary osteoclasts showed impaired spreading, adhesion, migration and resorption due to altered ß3 integrin sub-unit downstream signaling. In apparent accordance with these in vitro results, Sema4D deletion in sexually mature female mice led to a high bone mass phenotype due to defective bone resorption by osteoclasts. Mutant males, however, displayed normal bone mass and the female osteopetrotic phenotype was only detected at the onset of sexual maturity, indicating that, in vivo, this intrinsic osteoclast defect might be overcome in these mice. Using bone marrow cross transplantation, we confirmed that Sema4D controls bone resorption through an indirect mechanism. In addition, we show that Sema4D −/− mice were less fertile than their WT littermates. A decrease in Gnrh1 hypothalamic expression and a reduced number of ovarian follicles can explain this attenuated fertility. Interestingly, ovariectomy abrogated the bone resorption phenotype in Sema4D −/− mice, providing the evidence that the observed high bone mass phenotype is strictly dependent on ovarian function. Altogether, this study reveals that, in vivo, Sema4D is an indirect regulator of bone resorption, which acts via its effect on reproductive function.

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Section: Introductionmentioning

confidence: 99%

Control of Bone Resorption by Semaphorin 4D Is Dependent on Ovarian Function

et al. 2011

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“…For example, both estrogens and androgens are major regulators of bone formation, and their deficiency is associated with bone loss (7, 46). Similarly, osteocalcin, predominantly a bone protein, regulates optimal male fertility in mice and humans via the testosterone-pancreas-bone axis (47–49).…”

Section: Discussionmentioning

confidence: 99%

Follistatin-like 3 is a mediator of exercise-driven bone formation and strengthening

Nam

Perera

Gordon

et al. 2015

Bone

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Exercise is vital for maintaining bone strength and architecture. Follistatin like 3 (FSTL3), a member of Follistatin family, is a mechanosensitive protein upregulated in response to exercise and is involved in regulating musculoskeletal health, we investigated the potential role of FSTL3 in exercise-driven bone remodeling. Exercise-dependent regulation of bone structure and functions was compared in mice with global Fstl3 gene deletion (Fstl3−/−) and their age-matched Fstl3+/+ littermates. Mice were exercised by low-intensity treadmill walking. The mechanical properties and mineralization were determined by μCT, three-point bending test and sequential incorporation of calcein and alizarin complexone. ELISA, Western-blot analysis and qRT-PCR were used to analyze the regulation of FSTL3 and associated molecules in the serum specimens and tissues. Daily exercise significantly increased circulating FSTL3 levels in mice, rats and humans. Compared to age-matched littermates, Fstl3−/− mice exhibited significantly lower fracture tolerance, having greater stiffness, but lower strain at fracture and yield energy. Furthermore, increased levels of circulating FSTL3 in young mice paralleled greater strain at fracture compared to the lower levels of FSTL3 in older mice. More significantly, Fstl3−/− mice exhibited loss of mechanosensitivity and irresponsiveness to exercise-dependent bone formation as compared to their Fstl3+/+ littermates. In addition, FSTL3 gene deletion resulted in loss of exercise-dependent sclerostin regulation in osteocytes and osteoblasts, as compared to Fstl3+/+ osteocytes and osteoblasts, in vivo and in vitro. The data identifies FSTL3 as a critical mediator of exercise-dependent bone formation and strengthening and point to its potential role in bone health and in musculoskeletal diseases.

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“…In addition, the influence of the genetic, cellular, and external environment can have significant impacts on craniofacial development. For instance, sex hormones have drastic effects on embryonic facial patterning (Cohen, et al 2014), juvenile development (Fujita, et al 2004; Marquez Hernandez, et al 2011; Verdonck, et al 1998), and bone remodeling at juvenile and adult stages (Frenkel, et al 2010; Nicks, et al 2010). The hardness of diet can also have a significant impact on craniofacial geometry (Genbrugge, et al 2011; Parsons, et al 2014; Swiderski and Zelditch 2013).…”

Section: The Limitations Of Induced Mutationsmentioning

confidence: 99%

Cichlid fishes as a model to understand normal and clinical craniofacial variation

Powder

Albertson

2016

Developmental Biology

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We have made great strides towards understanding the etiology of craniofacial disorders, especially for ‘simple’ Mendelian traits. However, the facial skeleton is a complex trait, and the full spectrum of genetic, developmental, and environmental factors that contribute to its final geometry remain unresolved. Forward genetic screens are constrained with respect to complex traits due to the types of genes and alleles commonly identified, developmental pleiotropy, and limited information about the impact of environmental interactions. Here, we discuss how studies in an evolutionary model – African cichlid fishes – can complement traditional approaches to understand the genetic and developmental origins of complex shape. Cichlids exhibit an unparalleled range of natural craniofacial morphologies that model normal human variation, and in certain instance mimic human facial dysmorphologies. Moreover, the evolutionary history and genomic architecture of cichlids make them an ideal system to identify the genetic basis of these phenotypes via quantitative trait loci (QTL) mapping and population genomics. Given the molecular conservation of developmental genes and pathways, insights from cichlids are applicable to human facial variation and disease. We review recent work in this system, which has identified lbh as a novel regulator of neural crest cell migration, determined the Wnt and Hedgehog pathways mediate species-specific bone morphologies, and examined how plastic responses to diet modulate adult facial shapes. These studies have not only revealed new roles for existing pathways in craniofacial development, but have identified new genes and mechanisms involved in shaping the craniofacial skeleton. In all, we suggest that combining work in traditional laboratory and evolutionary models offers significant potential to provide a more complete and comprehensive picture of the myriad factors that are involved in the development of complex traits.

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Reproductive Hormones and Bone

Cited by 45 publications

References 52 publications

Control of Bone Resorption by Semaphorin 4D Is Dependent on Ovarian Function

Control of Bone Resorption by Semaphorin 4D Is Dependent on Ovarian Function

Follistatin-like 3 is a mediator of exercise-driven bone formation and strengthening

Cichlid fishes as a model to understand normal and clinical craniofacial variation

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