The role of estrogen receptor α in growth plate cartilage for longitudinal bone growth

2010 ◽  
Vol 25 (12) ◽  
pp. 2690-2700 ◽  
Author(s):  
Anna E Börjesson ◽  
Marie K Lagerquist ◽  
Chen Liu ◽  
Ruijin Shao ◽  
Sara H Windahl ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Growth Plate ◽  
Bone Growth ◽  
Estrogen Receptor Α ◽  
Longitudinal Bone Growth ◽  
Growth Plate Cartilage

scholarly journals The role of estrogen receptor-α and its activation function-1 for growth plate closure in female mice

2012 ◽  
Vol 302 (11) ◽  
pp. E1381-E1389 ◽  
Author(s):  
A. E. Börjesson ◽  
S. H. Windahl ◽  
E. Karimian ◽  
E. E. Eriksson ◽  
M. K. Lagerquist ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Growth Plate ◽  
Bone Growth ◽  
High Dose ◽  
Plate Height ◽  
Chondrocyte Proliferation ◽  
Growth Plates ◽  
Longitudinal Bone Growth ◽  
Female Mice

High estradiol levels in late puberty induce growth plate closure and thereby cessation of growth in humans. In mice, the growth plates do not fuse after sexual maturation, but old mice display reduced longitudinal bone growth and high-dose estradiol treatment induces growth plate closure. Estrogen receptor (ER)-α stimulates gene transcription via two activation functions (AFs), AF-1 and AF-2. To evaluate the role of ERα and its AF-1 for age-dependent reduction in longitudinal bone growth and growth plate closure, female mice with inactivation of ERα (ERα−/−) or ERαAF-1 (ERαAF-10) were evaluated. Old (16- to 19-mo-old) female ERα−/− mice showed continued substantial longitudinal bone growth, resulting in longer bones (tibia: +8.3%, P < 0.01) associated with increased growth plate height (+18%, P < 0.05) compared with wild-type (WT) mice. In contrast, the longitudinal bone growth ceased in old ERαAF-10 mice (tibia: −4.9%, P < 0.01). Importantly, the proximal tibial growth plates were closed in all old ERαAF-10 mice while they were open in all WT mice. Growth plate closure was associated with a significantly altered balance between chondrocyte proliferation and apoptosis in the growth plate. In conclusion, old female ERα−/− mice display a prolonged and enhanced longitudinal bone growth associated with increased growth plate height, resembling the growth phenotype of patients with inactivating mutations in ERα or aromatase. In contrast, ERαAF-1 deletion results in a hyperactive ERα, altering the chondrocyte proliferation/apoptosis balance, leading to growth plate closure. This suggests that growth plate closure is induced by functions of ERα that do not require AF-1 and that ERαAF-1 opposes growth plate closure.

The role of estrogen receptor α in the regulation of bone and growth plate cartilage

2013 ◽  
Vol 70 (21) ◽  
pp. 4023-4037 ◽  
Author(s):  
A. E. Börjesson ◽  
M. K. Lagerquist ◽  
S. H. Windahl ◽  
C. Ohlsson
Keyword(s):  
Estrogen Receptor ◽  
Growth Plate ◽  
Estrogen Receptor Α ◽  
Growth Plate Cartilage

scholarly journals Role of estrogen receptor signaling in skeletal response to leptin in female ob/ob mice

2017 ◽  
Vol 233 (3) ◽  
pp. 357-367 ◽  
Author(s):  
Russell T Turner ◽  
Kenneth A Philbrick ◽  
Amida F Kuah ◽  
Adam J Branscum ◽  
Urszula T Iwaniec
Keyword(s):  
Estrogen Receptor ◽  
Cancellous Bone ◽  
Bone Growth ◽  
Volume Fraction ◽  
Gonadal Hormones ◽  
Uterine Weight ◽  
Bone Formation Rate ◽  
Longitudinal Bone Growth ◽  
Gonadal Dysfunction

Leptin, critical in regulation of energy metabolism, is also important for normal bone growth, maturation and turnover. Compared to wild type (WT) mice, bone mass is lower in leptin-deficient ob/ob mice. Osteopenia in growing ob/ob mice is due to decreased bone accrual, and is associated with reduced longitudinal bone growth, impaired cancellous bone maturation and increased marrow adipose tissue (MAT). However, leptin deficiency also results in gonadal dysfunction, disrupting production of gonadal hormones which regulate bone growth and turnover. The present study evaluated the role of increased estrogen in mediating the effects of leptin on bone in ob/ob mice. Three-month-old female ob/ob mice were randomized into one of the 3 groups: (1) ob/ob + vehicle (veh), (2) ob/ob + leptin (leptin) or (3) ob/ob + leptin and the potent estrogen receptor antagonist ICI 182,780 (leptin + ICI). Age-matched WT mice received vehicle. Leptin (40 µg/mouse, daily) and ICI (10 µg/mouse, 2×/week) were administered by subcutaneous injection for 1 month and bone analyzed by X-ray absorptiometry, microcomputed tomography and static and dynamic histomorphometry. Uterine weight did not differ between ob/ob mice and ob/ob mice receiving leptin + ICI, indicating that ICI successfully blocked the uterine response to leptin-induced increases in estrogen levels. Compared to leptin-treated ob/ob mice, ob/ob mice receiving leptin + ICI had lower uterine weight; did not differ in weight loss, MAT or bone formation rate; and had higher longitudinal bone growth rate and cancellous bone volume fraction. We conclude that increased estrogen signaling following leptin treatment is dispensable for the positive actions of leptin on bone and may attenuate leptin-induced bone growth.

scholarly journals Effect of Clodronate Administration on the Structure of the Primary Spongiosa derived from the Growth Cartilage in Growing Rats

2019 ◽  
Vol 2 (1) ◽  
pp. 27-35
Author(s):  
Helena Gil-Peña ◽  
Ángela Fernández-Iglesias ◽  
Rocío Fuente ◽  
Laura Alonso-Duran ◽  
Fernando Santos ◽  
...  
Keyword(s):  
Growth Plate ◽  
Bone Growth ◽  
Blue Staining ◽  
Growth Spurt ◽  
Alcian Blue Staining ◽  
Tartrate Resistant Acid Phosphatase ◽  
Sprague Dawley ◽  
Proliferating Cells ◽  
Longitudinal Bone Growth ◽  
Growth Plate Cartilage

The effect of the inhibition of the resorptive activity of osteoclastic cells induced by bisphosphonate treatment on the primary spongiosa derived from the calcified cartilage of the growth plate was studied. We focused our attention on the primary spongiosa because it is the initial trabecular bone network that is first formed directly from growth plate mineralized cartilaginous septa. The study was carried out in male Sprague-Dawley rats at the age of 35 days, coinciding with the prepubertal growth spurt, a stage characterized by the highest values for growth rate. Animals were classified in two groups, controls and rats treated with clodronate 60 mg/kg/day. Body weights and tibial length were measured. The rate of longitudinal bone growth was obtained by calceine labelling and the height of the growth plate cartilage was measured. Histochemical analysis included Alcian blue staining, detection of tartrate-resistant acid phosphatise (TRAP) activity, von Kossa staining for mineralization and immunolocalization of proliferating cells. Microscopic examination revealed numerous tartrate-resistant acid phosphatase (TRAP)-positive cells at the chondroosseous junction and associated with subchondral trabeculae in control rat and that clodronate treatment induced a marked reduction of these cells. Clodronate-treated rats presented thinner subchondral trabeculae that were more irregularly oriented and decreased cell proliferation in the primary spongiosa. Results obtained showed that changes induced by clodronate treatment has little effect on the activity of the growth plate cartilage, without a significant effect on longitudinal bone growth even at doses much higher than those used in clinical practice.

scholarly journals The Role of the Growth Plate in Longitudinal Bone Growth

1991 ◽  
Vol 70 (8) ◽  
pp. 1806-1814 ◽  
Author(s):  
M. PINES ◽  
S. HURWITZ
Keyword(s):  
Growth Plate ◽  
Bone Growth ◽  
Longitudinal Bone Growth

scholarly journals DHEA Suppresses Longitudinal Bone Growth by Acting Directly at Growth Plate through Estrogen Receptors

Endocrinology ◽  
2011 ◽  
Vol 152 (4) ◽  
pp. 1423-1433 ◽  
Author(s):  
Hongzhi Sun ◽  
Weijin Zang ◽  
Bo Zhou ◽  
Lin Xu ◽  
Shufang Wu
Keyword(s):  
Estrogen Receptor ◽  
Growth Plate ◽  
Bone Growth ◽  
Nuclear Factor Κb ◽  
Binding Activity ◽  
Skeletal Maturation ◽  
Chondrocyte Apoptosis ◽  
Chondrocyte Proliferation ◽  
Longitudinal Bone Growth ◽  
Growth Plate Chondrocyte

Abstract Dehydroepiandrosterone (DHEA) is produced by the adrenal cortex and is the most abundant steroid in humans. Although in some physiological and pathological conditions the increased secretion of DHEA and its sulfated form is associated with accelerated growth rate and skeletal maturation, it is unclear whether DHEA can affect longitudinal bone growth and skeletal maturation by acting directly at the growth plate. In our study, DHEA suppressed metatarsal growth, growth plate chondrocyte proliferation, and hypertrophy/differentiation. In addition, DHEA increased the number of apoptotic chondrocytes in the growth plate. In cultured chondrocytes, DHEA reduced chondrocyte proliferation and induced apoptosis. The DHEA-induced inhibition of metatarsal growth and growth plate chondrocyte proliferation and hypertrophy/differentiation was nullified by culturing metatarsals with DHEA in the presence of ICI 182,780, an inhibitor of estrogen receptor, but not in the presence of Casodex, an inhibitor of androgen receptor. Lastly, nuclear factor-κB DNA binding activity was inhibited by the addition of DHEA in the medium of cultured chondrocyte. Our findings indicate that DHEA suppressed bone growth by acting directly at growth plate through estrogen receptor. Such growth inhibition is mediated by decreased chondrocyte proliferation and hypertrophy/differentiation and by increased chondrocyte apoptosis.

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