Inhbitors of cyclo-oxygenase-2 and secretory phospholipase A2 preserve bone architecture following ovariectomy in adult rats

Gregory, Laura S., Kelly, Wendy L., Reid, Robert R., Fairlie, David P., & Forwood, Mark R. (2006) Inhbitors of cyclo-oxygenase-2 and secretory phospholipase A2 preserve bone architecture following ovariectomy in adult rats. Bone, 39(1), pp. 134-142.

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Epidemiological evidence and in vitro data suggest that COX-2 is a key regulator of accelerated remodeling. Accelerated states of osteoblast and osteoclast activity are regulated by prostaglandins in vitro, but experimental evidence for specific roles of cyclooxygenase-2 (COX-2) and secretory phospholipase A2 (sPLA2) in bone adaptive remodeling in vivo is lacking. We found that treatment with a specific COX-2 or sPLA2 (group IIa) inhibitor prevented ovariectomy-induced (OVX-induced) decreases in trabecular connectivity; suppressed the acceleration of bone resorption; and maintained bone turnover at SHAM levels following OVX in the rat. The sPLA2 inhibitor significantly suppressed increases in osteoclast surface induced by OVX, whilst the COX-2 inhibitor only had a marginal effect. These findings demonstrate that specific inhibitors of COX-2 and sPLA2-IIa effectively suppress OVX-induced bone loss in the adult rat by conserving trabecular bone mass and architecture through reduced bone remodeling and decreased resorptive activity. Moreover we report an important role of sPLA2-IIa in osteoclastogenesis independent of the COX-2 metabolic pathway in the OVX rat in vivo.

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31 citations in Scopus
28 citations in Web of Science®
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ID Code: 4911
Item Type: Journal Article
Refereed: Yes
Keywords: arachidonic acid, bone remodeling, cyclooxygenase isoforms, phospholipase A2, osteoclasts
DOI: 10.1016/j.bone.2005.12.017
ISSN: 8756-3282
Subjects: Australian and New Zealand Standard Research Classification > PHYSICAL SCIENCES (020000)
Divisions: Past > QUT Faculties & Divisions > Faculty of Science and Technology
Copyright Owner: Copyright 2006 Elsevier
Copyright Statement: Reproduced in accordance with the copyright policy of the publisher.
Deposited On: 04 Sep 2006 00:00
Last Modified: 29 Feb 2012 14:12

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