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Estrogen receptor-beta modulates synthesis of bone matrix proteins in human osteoblast-like MG63 cells
- Source :
- Journal of cellular biochemistry. 89(1)
- Publication Year :
- 2003
-
Abstract
- Estrogens have complex effects on the skeleton, including regulation of modeling and maintenance of bone mass, which vary with cell type and developmental stage. Osteoblasts are key regulators of skeletal matrix synthesis and degradation. However, whether osteocytes, osteoblasts or earlier progenitors mediate estrogen effects, and the importance of estrogen receptors (ERs) alpha and beta, remain unclear. To address estrogen response in human cells closely related to secretory osteoblasts, we studied MG63 cells with ERalpha or ERbeta reduced to low levels by stable transfection of antisense plasmids. Collagen and alkaline phosphatase expression increased with estrogen in wild-type and ERalpha-suppressed cells, but not in ERbeta-suppressed cells. Matrix secretion occurs as osteoblasts cease dividing, and, in keeping with this, cell proliferation was reduced by estrogen except in ERbeta-antisense cells. No effects of estrogen on wild type or ER-suppressed cells were seen in expression of BMP 2, the BMP antagonist noggin, or Indian hedgehog, products that regulate differentiation of osteoblasts. In contrast to expectations that estrogen would modulate bone degradation, RANKL, CSF-1, and osteoprotegerin did not respond measurably to estrogen, regardless of ER status. In keeping with this result, estrogen response was not observed in assays of osteoclast development from CD14 cells supported by wild-type or ER-silenced MG63 cells. Since estrogens are major regulators of bone degradation in vivo, estrogen effects on osteoclasts may depend on interaction with stimuli present in bone but absent in the model studied. cDNA hybridization showed that additional estrogen-binding proteins including ERRalpha and BCAR3 were expressed by MG63, but estrogen effects in ERbeta-silenced cells were small, so these proteins are either minor regulators in MG63 cells, or act in concert with stimuli in addition to estrogen. We conclude that, in the MG63 cell line, estrogen increases synthesis of matrix proteins via ERbeta, and that, in the absence of additional stimuli, these cells are not major mediators of estrogen effects on osteoclast differentiation. Further, ERalpha is probably much more important in earlier stages of skeletal development, such as growth plate response, than in osteoblasts.
- Subjects :
- medicine.medical_specialty
medicine.drug_class
Cellular differentiation
Estrogen receptor
Bone Matrix
Bone Morphogenetic Protein 2
Osteoclasts
Biology
Transfection
Biochemistry
DNA, Antisense
Cell Line
Estrogen-related receptor
Osteoclast
Transforming Growth Factor beta
Internal medicine
medicine
Estrogen Receptor beta
Humans
RNA, Messenger
Molecular Biology
Estrogen receptor beta
Osteoblasts
Base Sequence
Estradiol
Estrogen Receptor alpha
Osteoblast
Cell Differentiation
Cell Biology
medicine.anatomical_structure
Endocrinology
Receptors, Estrogen
Estrogen
Bone Morphogenetic Proteins
Cytokines
Estrogen receptor alpha
hormones, hormone substitutes, and hormone antagonists
Subjects
Details
- ISSN :
- 07302312
- Volume :
- 89
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of cellular biochemistry
- Accession number :
- edsair.doi.dedup.....552e58c2ff80b2c964f1f6590b82457b