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Blocking antibody to the β-subunit of FSH prevents bone loss by inhibiting bone resorption and stimulating bone synthesis
- Source :
- Proceedings of the National Academy of Sciences of the United States of America. 109(36)
- Publication Year :
- 2012
-
Abstract
- Low estrogen levels undoubtedly underlie menopausal bone thinning. However, rapid and profuse bone loss begins 3 y before the last menstrual period, when serum estrogen is relatively normal. We have shown that the pituitary hormone FSH, the levels of which are high during late perimenopause, directly stimulates bone resorption by osteoclasts. Here, we generated and characterized a polyclonal antibody to a 13-amino-acid-long peptide sequence within the receptor-binding domain of the FSH β-subunit. We show that the FSH antibody binds FSH specifically and blocks its action on osteoclast formation in vitro. When injected into ovariectomized mice, the FSH antibody attenuates bone loss significantly not only by inhibiting bone resorption, but also by stimulating bone formation, a yet uncharacterized action of FSH that we report herein. Mesenchymal cells isolated from mice treated with the FSH antibody show greater osteoblast precursor colony counts, similarly to mesenchymal cells isolated from FSH receptor ( FSHR ) −/− mice. This suggests that FSH negatively regulates osteoblast number. We confirm that this action is mediated by signaling-efficient FSHRs present on mesenchymal stem cells. Overall, the data prompt the future development of an FSH-blocking agent as a means of uncoupling bone formation and bone resorption to a therapeutic advantage in humans.
- Subjects :
- medicine.medical_specialty
endocrine system
Ovariectomy
Osteoporosis
Osteoclasts
Biology
Bone resorption
Antibodies
Colony-Forming Units Assay
Follicle-stimulating hormone
Mice
Osteoclast
Internal medicine
Blocking antibody
medicine
Animals
Humans
Osteoporosis, Postmenopausal
Mice, Knockout
Multidisciplinary
Bone Development
Osteoblast
Mesenchymal Stem Cells
Biological Sciences
medicine.disease
Bone morphogenetic protein 7
medicine.anatomical_structure
Endocrinology
Follicle Stimulating Hormone, beta Subunit
Receptors, FSH
Female
Follicle-stimulating hormone receptor
hormones, hormone substitutes, and hormone antagonists
Subjects
Details
- ISSN :
- 10916490
- Volume :
- 109
- Issue :
- 36
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Accession number :
- edsair.doi.dedup.....c838ffee22f626952ffee44aa1fdb002