Effects of a beta 3 adrenergic receptor agonist on bone and bone marrow adipocytes in the tibia and lumbar spine of the ovariectomized rat.
The object of this study was to investigate the effects of a b3 adrenergic receptor agonist (ARa) and estrogen on bone remodeling and bone marrow adipocyte differentiation. Ten-week-old female Sprague-Dawley rats underwent sham operation (Sham) or were ovariectomized (OVX) and were divided into four groups: Sham, Sham+ARa, OVX, and OVX+ARa groups. They were given orally the b3-ARa, BRL 35135, or vehicle daily for 4 weeks and their tibial and lumbar spinal bone and fat histomorphometric parameters were measured. In tibial proximal metaphysis, the adipocyte number per bone marrow unit volume (N.A/MV), and the percent adipocyte volume (AV/MV) values of the OVX and OVX+ARa groups were significantly higher than the Sham and Sham+ARa groups (P = 0.004, P = 0.008 in OVX, respectively), but ARa administration had no effect on bone remodeling or adipocyte differentiation. N.A/MV and AV/MV correlated negatively with the bone volume (BV/TV, r = -0.67, P = 0.001; r = -0.62, P = 0.004, respectively), and they correlated with the bone resorption parameters, i.e., the eroded surface (ES/BS), osteoclast surface (Oc.S/BS), and osteoclast number (N.Oc/BS) in tibial proximal metaphysis. In tibial distal metaphysis, the adipocyte volume per cell (AV/N.A) values of the OVX and OVX+ARa groups were significantly higher than those of the Sham and Sham+ ARa group (P = 0.003 in OVX). In the lumbar spine, the AV/N.A values of the Sham+ARa and OVX+ARa groups were significantly lower than the Sham and OVX groups values (P < 0.0001 in ARa administration), but OVX did not affect adipocyte differentiation. Beta3-ARa administration affects the bone marrow adipocyte differentiation, which is site-specific difference, although mainly negative in the context of bone.
Kurabayashi
T
T
Department of Obstetrics and Gynecology, Niigata University School of Medicine, 1-757, Asahimachi-dori, Niigata-city, Niigata 951-8510, Japan.
Tomita
M
M
Matsushita
H
H
Honda
A
A
Takakuwa
K
K
Tanaka
K
K
D017667:Adipocytes / Q000187:drug effects*; D058667:Adrenergic beta-3 Receptor Agonists; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects*; D048429:Cell Size; D005260:Female; D008159:Lumbar Vertebrae / Q000187:drug effects*; D010052:Ovariectomy; D010627:Phenethylamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000187:drug effects*
D058667:Adrenergic beta-3 Receptor Agonists; D010627:Phenethylamines; C063157:BRL 35135