Purification of megakaryocyte differentiation activity from a human fibrous histiocytoma cell line: N-terminal sequence homology with activin A

Fujimoto, Koji; Kawakita, Makoto; Kato, Kazuharu; Yonemura, Yuji; Masuda, Tetsuya; Matsuzaki, Hiromitsu; Hirose, Jiro; Isaji, Mitsuko; Sasaki, Hideki; Inoue, Tohru; Takatsuki, Kiyoshi

doi:10.1016/0006-291x(91)91543-l

Cited by 21 publications

(10 citation statements)

References 12 publications

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“…Although inhibin ␣-subunit expression (required for inhibin dimer formation) is very low in human and rat bone marrow (14, 15), inhibin accumulates in the bone marrow of 25-d-old rats within 10 min of iv injection of [ 125 I]InhA and is retained for at least an hour (16). These results are consistent with the idea that the effects of inhibin on marrow cell hematopoiesis (17)(18)(19) are attributable to inhibin derived from gonadal sources (20). Collectively, these data led to our hypothesis that changes in the gonadal inhibins may have direct effects on osteoblast and osteoclast development, thereby regulating increases in bone turnover and bone mass.…”

supporting

confidence: 93%

Inhibin A Is an Endocrine Stimulator of Bone Mass and Strength

et al. 2007

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Gonadal function plays a major role in bone homeostasis. It is widely held that the skeletal consequences of hypogonadism are solely due to a loss of sex steroids; however, increases in bone turnover begin during perimenopause before decreases in serum estradiol levels. These data and our demonstration that inhibins acutely regulate bone cell differentiation in vitro led us to test whether inhibin A (InhA) regulates bone mass in vivo. Using a transgenic model of inducible human InhA expression, InhA increased total body bone mineral density, increased bone volume, and improved biomechanical properties at the proximal tibia in intact mice and also prevented the loss of BMD and bone volume and strength associated with gonadectomy at both the spine and proximal tibia. In addition, InhA increased mineral apposition rate, double-labeled surface, and serum osteocalcin levels in vivo and osteoblastogenesis ex vivo without affecting osteoclast number or activity. Together these results demonstrate novel stimulatory effects of InhA on the skeleton in vivo. These studies provide in vivo evidence demonstrating that gonadal factors other than sex steroids play an important role in regulating bone mass and strength and, combined with our previous clinical data, suggest that gonadal InhA may be a component of the normal endocrine repertoire that regulates bone quality in both the axial and appendicular skeleton.

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supporting

confidence: 93%

Inhibin A Is an Endocrine Stimulator of Bone Mass and Strength

et al. 2007

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supporting

confidence: 80%

Bone Turnover across the Menopause Transition: Correlations with Inhibins and Follicle-Stimulating Hormone

Perrien¹,

Achenbach²,

Bledsoe³

et al. 2006

The Journal of Clinical Endocrinology & Metabolism

101

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Context:Longitudinal clinical studies demonstrate that increases in bone turnover that occur in perimenopausal women correlate better with elevated serum FSH than with changes in serum estradiol (E2). This perimenopausal rise in FSH is due to a selective decrease in ovarian inhibin B (InhB). Our previous demonstration that inhibins suppress both osteoblast and osteoclast development suggests that changes in serum inhibins may regulate osteoblast and osteoclast differentiation and thereby bone turnover, independent of changes in sex steroids.Objective: The objective of this study was to determine whether decreased serum inhibin A (InhA) and InhB levels correlate with increases in markers of bone turnover in women across the menopause transition and to evaluate serum inhibins as better predictors of bone turnover markers across the menopause transition than FSH or bioavailable E2. Design:We studied a cross-sectional age-stratified population sample of 188 pre-and postmenopausal women not using oral contraceptives or hormone replacement therapy (age, 21-85 yr).Results: Serum InhA and InhB levels significantly correlated inversely with markers of bone formation and bone resorption in preand perimenopausal women and with markers of bone formation in postmenopausal women (InhA only). FSH was not significantly correlated with bone turnover in either pre-or postmenopausal women; however, FSH was significantly correlated with bone resorption (Cterminal collagen I cross-link) in perimenopausal women (age, 45-54 yr). Using multivariate analyses, serum InhA better predicted bone formation and resorption markers in premenopausal women than either FSH or bioavailable E2. I T IS WIDELY accepted that estrogen plays a critical role in the maintenance of bone homeostasis and that the cellular basis of bone loss in postmenopausal women results from derepression of both osteoblast and osteoclast development (1). The pathophysiology of postmenopausal osteoporosis involves the overproduction of osteoclasts relative to the integrally coupled increase in osteoblastogenesis, a process that also facilitates osteoclast development (2-4). ConclusionsEstrogen deficiency has been identified as a major risk factor for osteoporosis in women (1,5,6). Recent evidence suggests that estrogen deficiency may be responsible, not only for the rapid bone loss of the early postmenopausal phase, but may also be involved in the later slower phase of bone loss associated with aging (5,7,8). However, in late premenopausal women with normal circulating estrogen levels, clinical indices of increased bone turnover are already elevated (9). In fact, the endocrine parameter best correlated with increases in bone turnover in a large cohort of perimenopausal women is elevated serum FSH levels (9). Studies in perimenopausal women have demonstrated that the mechanism involved in this early rise in FSH is a selective decrease in inhibin B (InhB) secretion in the presence of normal levels of estradiol (E2), inhibin A (InhA), GnRH, and LH (10, 11). Because both InhA a...

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“…STAT proteins may therefore not be involved in mediating the activin A growth inhibitory signal in this system. Activin A was ®rst studied as an inducer of follicle stimulating hormone (FSH) release (Vale et al, 1986;Ling et al, 1986), and was later found to be a pleiotropic cytokine exhibiting a variety of di erent functions (Murata et al, 1988;Fujimoto et al, 1991;Asashima et al, 1990;Smith et al, 1990;van den Eijnder et al, 1990;Thomsen et al, 1990;Matzuk et al, 1995;Zipori et al, 1986;Brosh et al, 1995). Included among its biological functions are also induction of growth inhibition and cell death.…”

Section: Discussionmentioning

confidence: 99%