Bone morphogenetic protein 2 enhances PGE(2)-stimulated osteoclast formation in murine bone marrow cultures.
Bone morphogenetic protein 2 (BMP-2) is used clinically to stimulate bone formation and accelerate fracture repair. Adding prostaglandin (PG) E(2) or PGE(2) receptor agonists to BMP-2 has been proposed to improve BMP-2 efficacy. However, this may enhance bone resorption, since PGE(2) can increase receptor activator of NF-kappaB ligand (RANKL) expression and decrease osteoprotegerin (OPG) expression in osteoblasts, and the RANKL:OPG ratio is critical for osteoclast formation. We used bone marrow (BM) cultures and BM macrophage (BMM) cultures from outbred CD1 mice to examine effects on osteoclast formation of BMP-2 and PGE(2). In BM cultures, which contain both osteoblastic and osteoclastic lineage cells, BMP-2 (100 ng/ml) alone did not increase osteoclast formation but enhanced the peak response to PGE(2) by 1.6-9.6-fold. In BMM cultures, which must be treated with RANKL because they do not contain osteoblastic cells, BMP-2 did not increase osteoclast formation, with or without PGE(2). Our results suggest that BMP-2 can increase osteoclast formation in response to PGE(2) by increasing the RANKL:OPG ratio in osteoblasts, which may have therapeutic implications for the use of BMP-2.
Blackwell
Katherine A
KA
New England Musculoskeletal Institute, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT 06030, USA.
Hortschansky
Peter
P
Sanovic
Srdan
S
Choudhary
Shilpa
S
Raisz
Lawrence G
LG
Pilbeam
Carol C
CC
D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D002452:Cell Count; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; D011994:Recombinant Proteins; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D015232:Dinoprostone