PMID- 18848653 OWN - NLM STAT- MEDLINE DCOM- 20090128 LR - 20151119 IS - 1873-2763 (Electronic) IS - 1873-2763 (Linking) VI - 44 IP - 1 DP - 2009 Jan TI - Differential mRNA expression profiles in proximal tibia of aged rats in response to ovariectomy and low-Ca diet. PG - 46-52 LID - 10.1016/j.bone.2008.09.003 [doi] AB - Both ovariectomized animals and animals fed with Ca-depleted diets are commonly used in vivo models for the investigation of osteoporosis-related bone loss. The present study aimed to study the genomic responses of bone in aged female rats to ovariectomy and dietary Ca deficiency in these models. Aged (11 months old) Sprague-Dawley rats were subjected to bilateral ovariectomy or sham-operation and fed with diets containing different dietary Ca content (LCD, 0.1% Ca or HCD, 1.2% Ca) for 12 weeks. Serum and urine were collected for biochemical marker measurement, and tibias were collected for bone mineral density (BMD) analysis by pQCT as well as for gene expression analysis by real-time PCR. Ovariectomy increased serum N-telopeptides of bone type I collagen (NTx) levels in aged rats fed with HCD (P<0.05). In addition, ovariectomy reduced BMD and predicted bone strength of tibial proximal metaphysis in aged rats fed with either LCD or HCD. Dietary Ca deficiency did not alter serum bone-specific alkaline phosphatase (BAP) or NTx levels, but induced a loss of BMD at tibia proximal metaphysis in aged rats. Ovariectomy promoted the mRNA expression of alpha-1 type I collagen (COL), osteoprotegerin (OPG) and receptor activator of nuclear factor-kappa B ligand (RANKL); and inhibited the mRNA expression of cathepsin K and matrix metalloproteinase-9 (MMP-9) in the proximal tibia of aged rats. Low-Ca diet significantly up-regulated the mRNA expression of COL, core binding factor I (Cbfa1), OPG and carbonic anhydrase II (CAII) in proximal tibia of aged rats. Our study revealed that the genomic responses of bone in proximal tibia to ovariectomy and dietary Ca deficiency were different. The bone loss induced by ovariectomy appears to be mediated primarily by an increase in RANKL mRNA expression; whereas the induction by dietary Ca restriction might be mediated by the induction of carbonic anhydrase II expression. FAU - Zhang, Yan AU - Zhang Y AD - State Key Laboratory of Chinese Medicine and Molecular Pharmacology, Shenzhen, PR China. FAU - Dong, Xiao-Li AU - Dong XL FAU - Leung, Ping-Chung AU - Leung PC FAU - Wong, Man-Sau AU - Wong MS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080920 PL - United States TA - Bone JT - Bone JID - 8504048 RN - 0 (Biomarkers) RN - 0 (Calcium, Dietary) RN - 0 (Osteoprotegerin) RN - 0 (RANK Ligand) RN - 0 (RNA, Messenger) SB - IM MH - Aging/*genetics MH - Animals MH - Biomarkers/blood/urine MH - Calcium, Dietary/*pharmacology MH - *Diet MH - Female MH - *Gene Expression Profiling MH - Gene Expression Regulation/drug effects MH - Organ Specificity/drug effects MH - Osteoblasts/drug effects/metabolism MH - Osteoclasts/drug effects/metabolism MH - Osteoprotegerin/metabolism MH - *Ovariectomy MH - RANK Ligand/metabolism MH - RNA, Messenger/genetics/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Tibia/*drug effects/*metabolism MH - Tomography, X-Ray Computed MH - Weight Gain/drug effects EDAT- 2008/10/14 09:00 MHDA- 2009/01/29 09:00 CRDT- 2008/10/14 09:00 PHST- 2008/05/28 00:00 [received] PHST- 2008/08/22 00:00 [revised] PHST- 2008/09/09 00:00 [accepted] PHST- 2008/10/14 09:00 [pubmed] PHST- 2009/01/29 09:00 [medline] PHST- 2008/10/14 09:00 [entrez] AID - S8756-3282(08)00776-X [pii] AID - 10.1016/j.bone.2008.09.003 [doi] PST - ppublish SO - Bone. 2009 Jan;44(1):46-52. doi: 10.1016/j.bone.2008.09.003. Epub 2008 Sep 20.