Effect of ovarian steroid deficiency on oestrogen receptor α expression in bone

Journal of Bone and Mineral Research

Suswillo

Rawlinson

et al. 2004

Osteoblast-like cells in primary cultures derived from ER␣؊/؊ mice do not proliferate in response to mechanical strain, unlike those from their ER␣ ؉/؉ littermates. ER␣ ؊/؊ cells also lack strainrelated NO production and responsiveness to IGFs. Proliferative responsiveness to strain is rescued by transfection with functional ER␣. ER␣ number or function in bone cells may limit bones' adaptability to mechanical loading.Introduction: In vivo, bones' osteogenic response to mechanical loading involves proliferation of surface osteoblasts. This response is replicated in vitro and involves ERK-mediated activation of the estrogen receptor (ER) ␣ and upregulation of estrogen response element activity. This proliferative response can be blocked by selective estrogen receptor modulators and increased by transfection of additional ER␣. Materials and Methods:We have now investigated the mechanisms of ER involvement in osteoblast-like cells' early responses to strain by comparing the responses of primary cultures of these cells derived from homozygous ER␣ knockout (ERKO) mice (ER␣

Section: Introductionsupporting

confidence: 86%

Osteoblast-Like Cells From Estrogen Receptor α Knockout Mice Have Deficient Responses to Mechanical Strain

Journal of Bone and Mineral Research

Suswillo

Rawlinson

et al. 2004

“…ERα mRNA and protein were first documented in skeletal tissues in 1988 (69,70) . ERα expression subsequently has been identified in human osteoblasts and osteocytes in vivo (71–73) . Others have identified ERα in both active osteoblasts and lining cells on trabecular surfaces of human and rabbit specimens but have not detected ERα in osteocytes or osteoclasts of either species (74) .…”

Section: Discussionmentioning

confidence: 99%

The Effect of In Vivo Mechanical Loading on Estrogen Receptor α Expression in Rat Ulnar Osteocytes

Ehrlich

Noble

J of Bone & Mineral Res

et al. 2002

The presence of estrogen receptor ␣ (ER␣) in osteocytes was identified immunocytochemically in transverse sections from 560 to 860 m distal to the midshaft of normal neonatal and adult male and female rat ulnas (n ‫؍‬ 3 of each) and from adult male rat ulnas that had been exposed to 10 days of in vivo daily 10-minute periods of cyclic loading producing peak strains of either ؊3000 (n ‫؍‬ 3) or ؊4000 microstrain (n ‫؍‬ 5). Each animal ambulated normally between loading periods, and its contralateral ulna was used as a control. In animals in which limbs were subject to normal locomotor loading alone, 14 ؎1.2% SEM of all osteocytes in each bone section were ER␣ positive. There was no influence of either gender (p ‫؍‬ 0.725) or age (p ‫؍‬ 0.577) and no interaction between them (p ‫؍‬ 0.658). In bones in which normal locomotion was supplemented by short periods of artificial loading, fewer osteocytes expressed ER␣ (7.5 ؎ 0.91% SEM) than in contralateral control limbs, which received locomotor loading alone (14 ؎ 1.68% SEM; p ‫؍‬ 0.01; median difference, 6.43; 95% CI, 2.60, 10.25). The distribution of osteocytes expressing ER␣ was uniform across all sections and thus did not reflect local peak strain magnitude. This suggests that osteocytes respond to strain as a population, rather than as individual strain-responsive cells. These data are consistent with the hypothesis that ER␣ is involved in bone cells' responses to mechanical strain. High strains appear to decrease ER␣ expression. In osteoporotic bone, the high strains assumed to accompany postmenopausal bone loss may reduce ER␣ levels and therefore impair the capacity for appropriate adaptive remodeling. (J Bone Miner Res 2002;17:1646 -1655)

“…This is sufficiently low to suggest that ER number may impose a limit on the size of the cells' adaptive response to strain. Ankrom et al (44) and Hoyland et al (45) have shown that in humans, ER number is regulated by the circulating levels of estrogen, and Lim et al (46) report that in rat, cortical bone ER number is reduced after ovariectomy. This leads us to hypothesize that postmenopausal bone loss occurs despite continued functional activity because of reduced effectiveness of the strain‐related influence on adaptive remodeling arising from reduced ER number.…”

Section: Discussionmentioning

confidence: 99%

Mechanical Strain and Estrogen Activate Estrogen Receptor α in Bone Cells

Journal of Bone and Mineral Research

Sjöberg

Cheng

et al. 2001

110

Bone cells' early responses to estrogen and mechanical strain were investigated in the ROS 17/2.8 cell line. Immunoblotting with antiphosphorylated estrogen receptor ␣ (ER-␣) antibody showed that when these cells were exposed for 10 minutes to estrogen (10 ؊8 M) or a single period of cyclic dynamic strain (peak 3400 ⑀, 1Hz, 600 cycles), there was an increase in the intensity of a 66-kDa band, indicating phosphorylation of ser