The effects of androgen deficiency on murine bone remodeling and bone mineral density are mediated via cells of the osteoblastic lineage.
Both estrogens and androgens act on bone marrow stromal/osteoblastic cells to inhibit the production of local factors that promote osteoclast development. Based on this and the evidence that loss of sex steroids up-regulates not only osteoclastogenesis but also osteoblastogenesis, we have hypothesized that cells of the osteoblastic lineage are the mediators of the adverse effects of sex steroid deficiency on bone. To test this hypothesis, we used the senescence-accelerated mouse (SAMP6), a model of defective osteoblast development, and examined the effects of orchidectomy on static and dynamic histological features of bone remodeling and on bone mineral density. After orchidectomy in SAMP6 mice, the expected increases in osteoblast precursors, cancellous osteoclasts and osteoblasts, frequency of remodeling events, trabecular spacing, and rate of bone formation were absent or greatly attenuated. Moreover, whereas bone mineral density decreased in orchidectomized controls, it did not change in SAMP6. Our data indicate that when osteoblast development is defective, orchidectomy fails to result in bone loss. This evidence suggests that cells of the osteoblastic lineage are essential mediators of the changes in the rate of bone remodeling and loss of bone mass that ensue following loss of androgens.
Weinstein
R S
RS
Division of Endocrinology/Metabolism, McClellan Veterans Affairs Medical Center Geriatric Research, Education, and Clinical Center, University of Arkansas for Medical Sciences, Little Rock 72205, USA. rweinstein@medlan.uams.edu
Jilka
R L
RL
Parfitt
A M
AM
Manolagas
S C
SC
D000728:Androgens / Q000172:deficiency* / Q000502:physiology; D000818:Animals; D001835:Body Weight; D015519:Bone Density; D001854:Bone Marrow Cells; D016723:Bone Remodeling; D002452:Cell Count; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009919:Orchiectomy; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology
D000728:Androgens