國家衛生研究院 NHRI:Item 3990099045/4525

NHRI > Institute of Cellular and Systems Medicine > Chun-Chin Tony Liang(2004-2009) > Periodical Articles > Item 3990099045/4525

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/4525

Title:	A combination of subtherapeutic doses of chemically modified doxycycline (CMT-8) and a bisphosphonate (clodronate) inhibits bone loss in the ovariectomized rat: A dynamic histomorphometric and gene expression study
Authors:	Ramamurthy, NS;Bain, S;Liang, CT;Barnes, J;Llavaneras, A;Liu, Y;Puerner, D;Strachan, MJ;Golub, LM
Contributors:	Division of Gerontology Research
Abstract:	Recent studies have demonstrated that tetracyclines can reduce bone loss in the ovariectomized (OVX) rat model of osteoporosis. In the current study, a non-antimicrobial, chemically modified doxycycline (CMT-8), alone or in combination with a bisphosphonate (Clodronate), was evaluated in this model. Forty-two, 6month old. female rats were randomly assigned to the following groups, (6/ group): a) sham/vehicle, b) OVX/vehicle; c) OVX/1 mg/day CMT-8; d) OVX/2 mg/day CMT-8, e) OVX/1 mg/week Clodronate; and f) OVX/1 mg/day CMT-8 + 1 mg/week Clodronate, CMT-8 was administered by oral gavage, Clodronate injected S/C. Following sham surgery or OVX, the rats were treated for 90 days with CMT-8 or vehicle alone, injected at three different times with fluorochrome labels, the rats were sacrificed, and the tibiae excised for analysis by dynamic bone histomorphometry. Femurs were aseptically removed and analyzed for collagen, collagenase and osteopontin mRNAs by Northern and dot blot analysis. As expected, OVX decreased trabecular bone volume (BV/TV by 73.8% vs. sham p<.01), and also reduced trabecular thickness, numbers, and increased spacing. Done loss in the OVX animals was partially prevented with either 2 mg/day CMT-8 or 1 mg/wk Clodronate (p<.01), while the mg/day CMT-8 had no effect. Interestingly, the efficacy of the combination therapy of CMT-8 and Clodronate was significantly better than either treatment by itself; maintaining bone mass and structural indices at levels identical to sham values. OVX rats mRNA for collagen, collagenase and osteopontin were elevated indicating high-turnover bone loss. Only COMBO therapy significantly reduced the collagenase and osteopontin mRNA. In summary, CMT-8 mono-therapy (2 mg) alone partially inhibited bone loss in this animal model of osteoporosis. However, 1mgday (CMT-8) monotherapy had no effect on bone loss or bone mRNA levels and when combined with Clodronate, interacted to increase efficacy. Thus, a combination of a suboptimal dose of CMT-8 and a bisphosphonate appears to increase the amount of bone by suppressing resorption in a model of osteoporosis.
Date:	2001-02
Relation:	Current Medicinal Chemistry. 2001 Feb;8(3):295-303.
Link to:	http://www.ncbi.nlm.nih.gov/sites/entrez/11172684
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0929-8673&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000167178600009
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0035041658
Appears in Collections:	[Chun-Chin Tony Liang(2004-2009)] Periodical Articles

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