Effects of dietary restriction on appendicular bone in the SENCAR mouse.
Peptide hormones, cytokines, and growth factors regulate cellular metabolism by stimulating second messenger signal transduction cascades in target tissues. A mutation in the regulatory domain of protein kinase C (PKC) in SENCAR (sensitive to carcinogenesis) mice renders them extremely sensitive to diacylglycerol and phorbol esters, resulting in rapid growth, high free radical generation, carcinogenesis, and metabolic bone disease. Dietary restriction (DR) normalizes PKC and ameliorates adverse downstream effects, including carcinogenesis, in SENCAR mice. We hypothesized that DR sufficient to ameliorate carcinogenesis would prevent or delay the early onset of metabolic bone disease in SENCAR mice. Male mice were assigned to 1 of 4 feeding groups from 10 to 16 weeks of age (the critical period when metabolic bone disease develops): ad libitum (AL)-fed; AL antioxidant (0.07% thioproline)-fed; 40% DR; or 40% DR antioxidant-fed. Femoral bone mass was determined gravimetrically. Tibial total, cortical, and trabecular bone mineral density (BMD) were determined by quantitative computed tomography. Body weight, femoral bone mass, and tibial cortical BMD were lower in DR than in AL mice. However, tibial total and trabecular BMD were higher in DR than in AL mice. Serum calcitonin, the hormone that inhibits the osteoclastic bone resorption that is most notable in trabecular bone, was 2-fold higher in DR than in AL-fed mice. Dietary thioproline had no major effects. Thus, DR sufficient to ameliorate carcinogenesis in SENCAR mice did not prevent early-onset metabolic bone disease, but it had a beneficial effect on tibial trabecular BMD that occurred at the apparent expense of cortical BMD. DR in SENCAR mice was also associated with elevated serum calcitonin, which may inhibit osteoclastic resorption and account for trabecular bone conservation in this model. In conclusion, PKC or the downstream metabolic processes regulated by it appear to play previously unrecognized roles in the regulation of tibial trabecular BMD and serum calcitonin in SENCAR mice.
Brochmann Murray
E J
EJ
Geriatric Research, Education and Clinical Center, Veterans Affairs Greater Los Angeles Healthcare System, Sepulveda, CA 91343, USA.
Beamer
W G
WG
Duarte
M E
ME
Behnam
K
K
Grisanti
M S
MS
Murray
S S
SS
D000818:Animals; D001835:Body Weight / Q000502:physiology; D015519:Bone Density; D001846:Bone Development / Q000502:physiology*; D002116:Calcitonin / Q000097:blood; D004032:Diet; D004435:Eating / Q000502:physiology*; D005269:Femur / Q000033:anatomy & histology / Q000737:chemistry; D008297:Male; D051379:Mice; D018632:Mice, Inbred SENCAR; D015675:Osteocalcin / Q000097:blood; D011863:Radioimmunoassay; D013977:Tibia / Q000033:anatomy & histology / Q000737:chemistry; D014057:Tomography, X-Ray Computed
D015675:Osteocalcin; D002116:Calcitonin