Secreted phospholipase A2 type II is present in Paget's disease of bone and modulates osteoclastogenesis,apoptosis and bone resorption of human osteoclasts independently of its catalytic activity in vitro |
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| Institution: | 1. Division of Toxicology, Institute of Environmental Medicine Karolinska Institutet, Box 210 171 77 Stockholm, Sweden;2. MV Lomonosov Moscow State University, 119991 Moscow, Russia;1. Department of Histology & Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, School of Medicine, Jinan University, Guangzhou 510632, PR China;2. Division of Cell and Developmental Biology, University of Dundee, Dundee DD1 5EH, UK;3. Stem Cell and Regeneration Thematic Research Programme, School of Biomedical Sciences, Chinese University of Hong Kong, Shatin, Hong Kong;4. Institute of Fetal-Preterm Labor Medicine, Jinan University, Guangzhou 510632, PR China |
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| Abstract: | ObjectivesTo study the role of secreted phospholipase A2 (sPLA2) in the pathophysiology of human osteoclasts (OCs).MethodsImmunohistochemistry and sPLA2 inhibitors were to determine the localization of sPLA2 and its role in OCs biology.ResultssPLA2 is expressed by OCs from healthy fetal bone and OCs from Paget's disease but not in normal bone. Inhibition of sPLA2 greatly reduces in vitro osteoclastogenesis.DiscussionThe decrease in OCs formed could be attributed to a decline in the viability of CD14+ OC precursors as well as a reduced viability of mature OCs. Inhibition of sPLA2 strongly decreases bone resorption by OCs independently of actin cytoskeleton remodeling, probably also by reducing OCs viability.ConclusionHigh amounts of this enzyme are present in fetal and Pagetic bone samples. Inhibition of sPLA2 in vitro decreases osteoclastogenesis and OC activity and might constitute an interesting pharmacologic target for diseases with high bone turnover. |
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| Keywords: | Phospholipase A2 Osteoclasts Bone Paget's disease of bone |
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