Osteoclast differentiation induced by synthetic octacalcium phosphate through receptor activator of NF-kappaB ligand expression in osteoblasts.
Synthetic octacalcium phosphate (OCP) has a potential to enhance new bone formation and exhibits biodegradable characteristics when implanted in experimentally created bone defects. The precise mechanisms of OCP biodegradation remain unclear, though histological observations have revealed that bone-resorbing osteoclasts appear and resorb implanted OCP. To investigate how osteoclasts develop around implanted OCP, we examined osteoclast differentiation using OCP crystals in vitro. Coculturing of mouse bone marrow cells and osteoblasts in OCP-coated cell culture plates induced osteoclast differentiation, whereas that did not occur without coating. Further, addition of bone morphogenetic protein-2 significantly increased the number of osteoclasts in the OCP-coated wells. In the presence of OCP, osteoblasts expressed receptor activator of NF-kappaB ligand (RANKL), an osteoclast differentiation factor. In addition, when half of each culture well was coated with OCP, osteoclasts were formed in both coated and noncoated areas, suggesting that soluble factors mediate osteoclast differentiation induced by OCP. Also, calcium levels in culture medium were significantly decreased in the presence of OCP, while experimental reduction of calcium from 8.0 to 5.0 mg/dL significantly induced RANKL mRNA expression. These results suggest that OCP itself decreases calcium levels around implanted OCP, which induces osteoclast differentiation through RANKL expression by osteoblasts.
Takami
Masamichi
M
Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan.
Mochizuki
Ayako
A
Yamada
Atsushi
A
Tachi
Keita
K
Zhao
Baohong
B
Miyamoto
Yoichi
Y
Anada
Takahisa
T
Honda
Yoshitomo
Y
Inoue
Tomio
T
Nakamura
Masanori
M
Suzuki
Osamu
O
Kamijo
Ryutaro
R
D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002130:Calcium Phosphates / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects*; D048430:Cell Shape / Q000187:drug effects; D018920:Coculture Techniques; D003460:Crystallization; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects*; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012995:Solubility / Q000187:drug effects
D055396:Bone Morphogenetic Protein 2; D002130:Calcium Phosphates; D053245:RANK Ligand; D012333:RNA, Messenger; C022045:octacalcium phosphate; D002118:Calcium