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Published on: June 8, 2014
Androgen receptors in bone-forming tissue
B Noble1, J Routledge, H Stevens
1University of Cambridge School of Clinical Medicine (Bone Research Group), Level 4, Addenbrooke's Hospital, Cambridge, UK.
Insights
Androgen receptors (AR) are present in human growth plates and osteoblasts. AR translocation to the nucleus in osteoblasts may depend on differentiation and culture conditions.
Area of Science:
- Endocrinology
- Cell Biology
- Orthopedics
Background:
- Androgen receptors (AR) play a role in various physiological processes.
- Understanding AR localization and function in bone cells is crucial for skeletal development and health.
Purpose of the Study:
- To investigate the presence and localization of androgen receptors in human growth plate chondrocytes and osteoblasts.
- To examine the translocation of AR into the nucleus of osteoblasts in response to androgens.
Main Methods:
- Immunohistochemical staining of AR in human growth plate sections and cultured osteoblasts.
- Culturing human osteoblasts with androgens (5alpha-dihydrotestosterone, methyltrienolone) and assessing AR localization via microscopy.
Main Results:
- AR were predominantly found in the cytoplasm of chondrocytes in the human growth plate.
- Osteoblasts and osteocytes exhibited numerous AR, primarily in the cytoplasm.
- Androgen stimulation induced AR translocation into the nucleus in osteoblasts from some, but not all, specimens.
Conclusions:
- Androgen receptors are present in human growth plate chondrocytes and osteoblasts.
- Osteoblasts derived from osteoarthritic patients show AR translocation to the nucleus upon androgen exposure.
- The capacity for AR nuclear translocation in osteoblasts may be influenced by cellular differentiation and culture conditions.
Abstract:
Androgen receptors (AR) were stained in sections of normal human growth plate of the costo sternal junction obtained at postmortem from one 4-day-old and two 5-day-old male infants, and in osteoblasts, grown in culture obtained from the femora of 3 male patients undergoing orthopaedic surgery for osteoarthritis. In the growth plate AR were found mostly in a narrow band of chondrocytes occupying an area about midway between the proximal and distal end of the epiphysis. Nearly all AR were in the cytoplasm and appeared in a granular form; there was no diffuse staining and the nuclei were either completely devoid of AR or only contained a few. Less-differentiated chondroblasts, perichondrial cells and hypertrophic chondrocytes contained few or no AR. Osteoblasts (and osteocytes) contained numerous AR and almost all were in the cytoplasm. Normal human osteoblasts, in their second or third passage, were grown on coverslips either in a medium with no added androgen or in the presence of 5alpha-dihydrotestosterone or methyltrienolone for a period of 24 h or longer. In control cultures, with vehicle and no added androgen, nearly all AR were found in the cytoplasm, with hardly any in the nucleus. In the presence of added androgen some osteoblasts from two of the specimens demonstrated a clear translocation of AR into the nucleus, whilst osteoblasts from a third specimen failed to translocate. These preliminary results indicate that AR translocation to the nucleus occurs in osteoblastic cells derived from osteoarthritic subjects. However, the ability to translocate may depend on the state of differentiation of the osteoblast and on culture conditions.
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