scholarly journals The Role of Estrogen Receptor α in Response to Longitudinal Bone Growth in ob/ob Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Lin-Yu Jin ◽  
Chen Guo ◽  
Shuai Xu ◽  
Hai-Ying Liu ◽  
Xin-Feng Li
Keyword(s):  
Growth Plate ◽  
Bone Growth ◽  
Expression Patterns ◽  
Plain Film ◽  
Growth Patterns ◽  
Endochondral Bone Formation ◽  
Specific Expression ◽  
X Ray ◽  
Longitudinal Bone Growth ◽  
Leptin Deficiency

The absence of leptin results in contrasting growth pattern of appendicular and axial bone growth in ob/ob mice. Endochondral bone formation is an important procedure of growth plate determining the bone growth, where this procedure is also regulated by estrogen and its receptor (ER) signaling pathway. The present study is undertaken to explore the roles of ERs in regulating the different growth patterns in ob/ob mice. In this study, C57BL/6 female mice were used as wild-type (WT) mice; ob/ob mice and WT mice were age-matched fed, and bone length is analyzed by X-ray plain film at the 12 weeks old. We confirm that ob/ob mice have shorter femoral length and longer spine length than WT mice (p < 0.05). The contrasting expression patterns of chondrocyte proliferation proteins and hypertrophic marker proteins are also observed from the femur and spinal growth plate of ob/ob mice compared with WT mice (p < 0.01). Spearman’s analysis showed that body length (axial and appendicular length) is positively related to the expression level of ERα in growth plate. Three-week-old female ob/ob mice are randomized divided into three groups: 1) ob/ob + ctrl, 2) ob/ob + ERα antagonist (MPP), and 3) ob/ob + ERβ antagonist (PHTPP). Age-matched C57BL/6 mice were also divided into three groups, same as the groups of ob/ob mice. MPP and PHTPP were administered by intraperitoneal injection for 6 weeks. However, the results of X-ray and H&E staining demonstrate that leptin deficiency seems to disturb the regulating effects of ER antagonists on longitudinal bone growth. These findings suggested that region-specific expression of ERα might be associated with contrasting phenotypes of axial and appendicular bone growth in ob/ob mice. However, ER signaling on longitudinal bone growth was blunted by leptin deficiency in ob/ob mice, and the underlying association between ERs and leptin needs to be explored in future work.

scholarly journals RECENT RESEARCH ON THE GROWTH PLATE: Recent insights into the regulation of the growth plate

2014 ◽  
Vol 53 (1) ◽  
pp. T1-T9 ◽  
Author(s):  
Julian C Lui ◽  
Ola Nilsson ◽  
Jeffrey Baron
Keyword(s):  
Growth Plate ◽  
Bone Morphogenetic Proteins ◽  
Bone Growth ◽  
Association Studies ◽  
Expression Patterns ◽  
Human Growth ◽  
Cytokine Signaling ◽  
Genome Wide Association Studies ◽  
Paracrine Factors ◽  
Large Numbers

For most bones, elongation is driven primarily by chondrogenesis at the growth plates. This process results from chondrocyte proliferation, hypertrophy, and extracellular matrix secretion, and it is carefully orchestrated by complex networks of local paracrine factors and modulated by endocrine factors. We review here recent advances in the understanding of growth plate physiology. These advances include new approaches to study expression patterns of large numbers of genes in the growth plate, using microdissection followed by microarray. This approach has been combined with genome-wide association studies to provide insights into the regulation of the human growth plate. We also review recent studies elucidating the roles of bone morphogenetic proteins, fibroblast growth factors, C-type natriuretic peptide, and suppressor of cytokine signaling in the local regulation of growth plate chondrogenesis and longitudinal bone growth.

Fluoride Inhibits Longitudinal Bone Growth by Acting Directly at the Growth Plate in Cultured Neonatal Rat Metatarsal Bones

2019 ◽  
Vol 197 (2) ◽  
pp. 522-532 ◽  
Author(s):  
Rui Ma ◽  
Shuang Liu ◽  
Tingting Qiao ◽  
Demin Li ◽  
Ruixue Zhang ◽  
...  
Keyword(s):  
Growth Plate ◽  
Bone Growth ◽  
Neonatal Rat ◽  
Longitudinal Bone Growth ◽  
Metatarsal Bones

scholarly journals Nuclear Factor-κB p65 Facilitates Longitudinal Bone Growth by Inducing Growth Plate Chondrocyte Proliferation and Differentiation and by Preventing Apoptosis

2007 ◽  
Vol 282 (46) ◽  
pp. 33698-33706 ◽  
Author(s):  
Shufang Wu ◽  
Janna K. Flint ◽  
Geoffrey Rezvani ◽  
Francesco De Luca
Keyword(s):  
Growth Plate ◽  
Bone Growth ◽  
Chondrocyte Apoptosis ◽  
Pyrrolidine Dithiocarbamate ◽  
Growth Plate Chondrocytes ◽  
Chondrocyte Proliferation ◽  
Longitudinal Bone Growth ◽  
Metatarsal Bones ◽  
Proliferation And Differentiation ◽  
Cultured Chondrocytes

NF-κB is a group of transcription factors involved in cell proliferation, differentiation, and apoptosis. Mice deficient in the NF-κB subunits p50 and p52 have retarded growth, suggesting that NF-κB is involved in bone growth. Yet, it is not clear whether the reduced bone growth of these mice depends on the lack of NF-κB activity in growth plate chondrocytes. Using cultured rat metatarsal bones and isolated growth plate chondrocytes, we studied the effects of two NF-κB inhibitors (pyrrolidine dithiocarbamate (PDTC) or BAY11-7082 (BAY)), p65 short interference RNA (siRNA), and of the overexpression of p65 on chondrocyte proliferation, differentiation, and apoptosis. To further define the underlying mechanisms, we studied the functional interaction between NF-κB p65 and BMP-2 in chondrocytes. PDTC and BAY suppressed metatarsal linear growth. Such growth inhibition resulted from decreased chondrocyte proliferation and differentiation and from increased chondrocyte apoptosis. In cultured chondrocytes, the inhibition of NF-κB p65 activation (by PDTC and BAY) and expression (by p65 siRNA) led to the same findings observed in cultured metatarsal bones. In contrast, overexpression of p65 in cultured chondrocytes induced chondrocyte proliferation and differentiation and prevented apoptosis. Although PDTC, BAY, and p65 siRNA reduced the expression of BMP-2 in cultured growth plate chondrocytes, the overexpression of p65 increased it. The addition of Noggin, a BMP-2 antagonist, neutralized the stimulatory effects of p65 on chondrocyte proliferation and differentiation, as well as its anti-apoptotic effect. In conclusion, our findings indicate that NF-κB p65 expressed in growth plate chondrocytes facilitates growth plate chondrogenesis and longitudinal bone growth by inducing BMP-2 expression and activity.

scholarly journals Estrogen stimulates leptin receptor expression in ATDC5 cells via the estrogen receptor and extracellular signal-regulated kinase pathways

2012 ◽  
Vol 213 (2) ◽  
pp. 163-172 ◽  
Author(s):  
Shan-Jin Wang ◽  
Xin-Feng Li ◽  
Lei-Sheng Jiang ◽  
Li-Yang Dai
Keyword(s):  
Growth Plate ◽  
Cross Talk ◽  
Bone Growth ◽  
Leptin Receptor ◽  
Receptor Expression ◽  
Long Bone ◽  
Endochondral Bone Formation ◽  
Dependent Manner ◽  
Growth Plate Chondrocytes ◽  
Concentration Dependent Manner

Regulation of the physiological processes of endochondral bone formation during long bone growth is controlled by various factors including the hormones estrogen and leptin. The effects of estrogen are mediated not only through the direct activity of estrogen receptors (ERs) but also through cross talk with other signaling systems implicated in chondrogenesis. The receptors of both estrogen and leptin (OBR (LEPR)) are detectable in growth plate chondrocytes of all zones. In this study, the expression of mRNA and protein of OBR in chondrogenic ATDC5 cells and the effect of 17β-estradiol (E2) stimulation were assessed using quantitative PCR and western blotting. We have found that the mRNA of Obr was dynamically expressed during the differentiation of ATDC5 cells over 21 days. Application of E2 (10−7 M) at day 14 for 48 h significantly upregulated OBR mRNA and protein levels (P<0.05). The upregulation of Obr mRNA by E2 was shown to take place in a concentration-dependent manner, with a concentration of 10−7 M E2 having the greatest effect. Furthermore, we have confirmed that E2 affected the phosphorylation of ERK1/2 (MAPK1/MAPK3) in a time-dependent manner where a maximal fourfold change was observed at 10 min following application of E2. Finally, pretreatment of the cells with either U0126 (ERK1/2 inhibitor) or ICI 182 780 (ER antagonist) blocked the upregulation of OBR by E2 and prevented the E2-induced phosphorylation of ERK. These data demonstrate, for the first time, the existence of cross talk between estrogen and OBR in the regulation of bone growth whereby estrogen regulates the expression of Obr in growth plate chondrocytes via ERs and the activation of ERK1/2 signaling pathways.

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.

Part 2. Review and meta‐analysis of studies on modulation of longitudinal bone growth and growth plate activity: A micro‐scale perspective

2021 ◽  
Author(s):  
Christian R. D'Andrea ◽  
Ausilah Alfraihat ◽  
Anita Singh ◽  
Jason B. Anari ◽  
Patrick J. Cahill ◽  
...  
Keyword(s):  
Growth Plate ◽  
Bone Growth ◽  
Meta Analysis ◽  
Longitudinal Bone Growth ◽  
Micro Scale
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