Search Results
You are looking at 1 - 3 of 3 items for
- Author: Andrei S Chagin x
- Refine by access: All content x
Search for other papers by Terhi J Heino in
Google Scholar
PubMed
Search for other papers by Andrei S Chagin in
Google Scholar
PubMed
Search for other papers by Lars Sävendahl in
Google Scholar
PubMed
Estrogens have significant impact on bone mineral metabolism. Besides the classical estrogen receptors (ERα and ERβ), a trans-membrane G-protein-coupled receptor (GPR30) has been demonstrated to mediate estrogenic effects. We aimed to study whether GPR30 is expressed in bone cells and if so, whether the level of expression is developmentally regulated. Metaphyseal bone biopsies were collected from the tibia in 14 boys and 6 girls, all at different stages of puberty. GPR30 protein expression was studied by immunohistochemistry in paraffin-embedded sections. GPR30-positive osteocytes and osteoblasts were quantified and linear regression analysis was applied. Cytoplasmic GPR30 expression was detected in osteoblasts, osteocytes, and osteoclasts. Osteocytes were more frequently positive for GPR30 than osteoblasts (58±4% vs 46±3% positive cells respectively, P<0.05). Detailed analysis demonstrated that GPR30 positivity declined during pubertal development in osteocytes (R=−0.56, P<0.01) but not in osteoblasts (R=−0.31, P>0.05). No sex difference was observed in the numbers of GPR30-positive osteoblasts or osteocytes. Furthermore, GPR30 expression did not correlate with chronological or bone age. In conclusion, the novel ER GPR30 is expressed in osteoblasts, osteocytes, and osteoclasts suggesting that non-genomic estrogen signaling via GPR30 may exist in bone. However, the functional role of GPR30 in bone tissue remains to be elucidated.
Search for other papers by Andrei S Chagin in
Google Scholar
PubMed
Search for other papers by Elham Karimian in
Google Scholar
PubMed
Search for other papers by Katja Sundström in
Google Scholar
PubMed
Search for other papers by Emma Eriksson in
Google Scholar
PubMed
Search for other papers by Lars Sävendahl in
Google Scholar
PubMed
Children exposed to systemic glucocorticoids often exhibit growth retardation and after the cessation of therapy catch-up growth occurs in many, but not all patients. The developmental regulation and underlying cellular mechanisms of catch-up growth are not fully understood. To clarify this issue, we established an in vitro model of catch-up growth. Here we present a protocol for the long-term culture (up to 160 days) of fetal (E20) as well as postnatal (P8) rat metatarsal bones which allowed us to characterize ex vivo the phenomenon of catch-up growth without any influence by systemic factors. The relevance of the model was confirmed by the demonstration that the growth of fetal and postnatal bones were stimulated by IGF1 (100 ng/ml) and inhibited by dexamethasone (Dexa; 1 μM). We found that the capacity to undergo catch-up growth was restricted to postnatal bones. Catch-up growth occurred after postnatal bones had been exposed to Dexa for 7 or 12 days but not after a more prolonged exposure (19 days). Incomplete catch-up growth resulted in compromised bone length when assessed at the end of the 4-month period of culture. While exposure to Dexa was associated with decreased chondrocyte proliferation and differentiation, catch-up growth was only associated with increased cell proliferation. We conclude that the phenomenon of catch-up growth after Dexa treatment is intrinsic to the growth plate and primarily mediated by an upregulation of chondrocyte proliferation.
Search for other papers by Joyce Emons in
Google Scholar
PubMed
Search for other papers by Andrei S Chagin in
Google Scholar
PubMed
Search for other papers by Torun Malmlöf in
Google Scholar
PubMed
Search for other papers by Magnus Lekman in
Google Scholar
PubMed
Search for other papers by Åsa Tivesten in
Google Scholar
PubMed
Search for other papers by Claes Ohlsson in
Google Scholar
PubMed
Search for other papers by Jan M Wit in
Google Scholar
PubMed
Department of Paediatrics, Department of Women's and Children's Health, Division of Endocrinology, Department of Tissue Regeneration, Department of Endocrinology and Metabolism, Leiden University Medical Center, 2300 ZA Leiden, The Netherlands
Search for other papers by Marcel Karperien in
Google Scholar
PubMed
Search for other papers by Lars Sävendahl in
Google Scholar
PubMed
Longitudinal bone growth is regulated in the growth plate. At the end of puberty, growth velocity diminishes and eventually ceases with the fusion of the growth plate through mechanisms that are not yet completely understood. Vascular endothelial growth factor (VEGF) has an important role in angiogenesis, but also in chondrocyte differentiation, chondrocyte survival, and the final stages of endochondral ossification. Estrogens have been shown to up-regulate VEGF expression in the uterus and bone of rats. In this study, we investigated the relation between estrogens and VEGF production in growth plate chondrocytes both in vivo and in vitro. The expression of VEGF protein was down-regulated upon ovariectomy and was restored upon estradiol (E2) supplementation in rat growth plates. In cultured rat chondrocyte cell line RCJ3.1C5.18, E2 dose dependently stimulated 121 and 189 kDa isoforms of VEGF, but not the 164 kDa isoform. Finally, VEGF expression was observed at both protein and mRNA levels in human growth plate specimens. The protein level increased during pubertal development, supporting a link between estrogens and local VEGF production in the growth plate. We conclude that estrogens regulate VEGF expression in the epiphyseal growth plate, although the precise role of VEGF in estrogen-mediated growth plate fusion remains to be clarified.
