Anti-c-fms Antibody Prevents Osteoclast Formation and Bone Resorption in Co-Culture of Osteoblasts and Osteoclast Precursors In Vitro and in Ovariectomized Mice

Osteoporosis morphology is characterized by bone resorption and decreases in micro-architecture parameters. Anti-osteoporosis therapy targets osteoclasts because bone resorption is a unique function of osteoclasts. Anti-c-fms antibodies against the receptor for macrophage colony-stimulating factor (...

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Main Authors: Yasuhiko Nara, Hideki Kitaura, Saika Ogawa, Wei-Ren Shen, Jiawei Qi, Fumitoshi Ohori, Takahiro Noguchi, Aseel Marahleh, Adya Pramusita, Ria Kinjo, Itaru Mizoguchi
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Language:English
Published: MDPI AG 2020-08-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/21/17/6120
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author Yasuhiko Nara
Hideki Kitaura
Saika Ogawa
Wei-Ren Shen
Jiawei Qi
Fumitoshi Ohori
Takahiro Noguchi
Aseel Marahleh
Adya Pramusita
Ria Kinjo
Itaru Mizoguchi
author_facet Yasuhiko Nara
Hideki Kitaura
Saika Ogawa
Wei-Ren Shen
Jiawei Qi
Fumitoshi Ohori
Takahiro Noguchi
Aseel Marahleh
Adya Pramusita
Ria Kinjo
Itaru Mizoguchi
author_sort Yasuhiko Nara
collection DOAJ
description Osteoporosis morphology is characterized by bone resorption and decreases in micro-architecture parameters. Anti-osteoporosis therapy targets osteoclasts because bone resorption is a unique function of osteoclasts. Anti-c-fms antibodies against the receptor for macrophage colony-stimulating factor (M-CSF) inhibit osteoclast formation and bone resorption in vitro and in vivo. However, the effect of anti-c-fms antibodies on bone resorption in ovariectomized (OVX) mice is unknown. In this study, we evaluated the effect of anti-c-fms antibodies on osteoclast formation and bone resorption in osteoblast–osteoclast precursor co-culture in vitro and in OVX mice. Osteoblast and osteoclast precursor co-cultures treated with anti-c-fms antibodies showed significantly inhibited osteoclast formation, while cultures without anti-c-fms antibody treatment showed osteoclast formation. However, anti-c-fms antibodies did not change the receptor activator of nuclear factor kappa-B ligand (RANKL) or osteoprotegrin (OPG) expression during osteoblast and osteoclast differentiation in vitro. These results indicate that anti-c-fms antibodies directly affected osteoclast formation from osteoclast precursors in co-culture. OVX mice were treated with intraperitoneal injections of anti-c-fms antibody. The trabecular bone structure of the femur was assessed by micro-computer tomography. The anti-c-fms antibody inhibited osteoclast formation and bone loss compared with PBS-treated OVX mice. These results indicate potential for the therapeutic application of anti-c-fms antibodies for postmenopausal osteoporosis.
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spelling doaj.art-c26a763adfad42a199a12f3cf104b1e72023-11-20T11:18:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-08-012117612010.3390/ijms21176120Anti-c-fms Antibody Prevents Osteoclast Formation and Bone Resorption in Co-Culture of Osteoblasts and Osteoclast Precursors In Vitro and in Ovariectomized MiceYasuhiko Nara0Hideki Kitaura1Saika Ogawa2Wei-Ren Shen3Jiawei Qi4Fumitoshi Ohori5Takahiro Noguchi6Aseel Marahleh7Adya Pramusita8Ria Kinjo9Itaru Mizoguchi10Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, Aoba-ku, Sendai, Miyagi 980–8575, JapanDivision of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, Aoba-ku, Sendai, Miyagi 980–8575, JapanDivision of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, Aoba-ku, Sendai, Miyagi 980–8575, JapanDivision of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, Aoba-ku, Sendai, Miyagi 980–8575, JapanDivision of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, Aoba-ku, Sendai, Miyagi 980–8575, JapanDivision of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, Aoba-ku, Sendai, Miyagi 980–8575, JapanDivision of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, Aoba-ku, Sendai, Miyagi 980–8575, JapanDivision of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, Aoba-ku, Sendai, Miyagi 980–8575, JapanDivision of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, Aoba-ku, Sendai, Miyagi 980–8575, JapanDivision of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, Aoba-ku, Sendai, Miyagi 980–8575, JapanDivision of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, Aoba-ku, Sendai, Miyagi 980–8575, JapanOsteoporosis morphology is characterized by bone resorption and decreases in micro-architecture parameters. Anti-osteoporosis therapy targets osteoclasts because bone resorption is a unique function of osteoclasts. Anti-c-fms antibodies against the receptor for macrophage colony-stimulating factor (M-CSF) inhibit osteoclast formation and bone resorption in vitro and in vivo. However, the effect of anti-c-fms antibodies on bone resorption in ovariectomized (OVX) mice is unknown. In this study, we evaluated the effect of anti-c-fms antibodies on osteoclast formation and bone resorption in osteoblast–osteoclast precursor co-culture in vitro and in OVX mice. Osteoblast and osteoclast precursor co-cultures treated with anti-c-fms antibodies showed significantly inhibited osteoclast formation, while cultures without anti-c-fms antibody treatment showed osteoclast formation. However, anti-c-fms antibodies did not change the receptor activator of nuclear factor kappa-B ligand (RANKL) or osteoprotegrin (OPG) expression during osteoblast and osteoclast differentiation in vitro. These results indicate that anti-c-fms antibodies directly affected osteoclast formation from osteoclast precursors in co-culture. OVX mice were treated with intraperitoneal injections of anti-c-fms antibody. The trabecular bone structure of the femur was assessed by micro-computer tomography. The anti-c-fms antibody inhibited osteoclast formation and bone loss compared with PBS-treated OVX mice. These results indicate potential for the therapeutic application of anti-c-fms antibodies for postmenopausal osteoporosis.https://www.mdpi.com/1422-0067/21/17/6120osteoclastOVXanti-c-fms antibodyM-CSF
spellingShingle Yasuhiko Nara
Hideki Kitaura
Saika Ogawa
Wei-Ren Shen
Jiawei Qi
Fumitoshi Ohori
Takahiro Noguchi
Aseel Marahleh
Adya Pramusita
Ria Kinjo
Itaru Mizoguchi
Anti-c-fms Antibody Prevents Osteoclast Formation and Bone Resorption in Co-Culture of Osteoblasts and Osteoclast Precursors In Vitro and in Ovariectomized Mice
International Journal of Molecular Sciences
osteoclast
OVX
anti-c-fms antibody
M-CSF
title Anti-c-fms Antibody Prevents Osteoclast Formation and Bone Resorption in Co-Culture of Osteoblasts and Osteoclast Precursors In Vitro and in Ovariectomized Mice
title_full Anti-c-fms Antibody Prevents Osteoclast Formation and Bone Resorption in Co-Culture of Osteoblasts and Osteoclast Precursors In Vitro and in Ovariectomized Mice
title_fullStr Anti-c-fms Antibody Prevents Osteoclast Formation and Bone Resorption in Co-Culture of Osteoblasts and Osteoclast Precursors In Vitro and in Ovariectomized Mice
title_full_unstemmed Anti-c-fms Antibody Prevents Osteoclast Formation and Bone Resorption in Co-Culture of Osteoblasts and Osteoclast Precursors In Vitro and in Ovariectomized Mice
title_short Anti-c-fms Antibody Prevents Osteoclast Formation and Bone Resorption in Co-Culture of Osteoblasts and Osteoclast Precursors In Vitro and in Ovariectomized Mice
title_sort anti c fms antibody prevents osteoclast formation and bone resorption in co culture of osteoblasts and osteoclast precursors in vitro and in ovariectomized mice
topic osteoclast
OVX
anti-c-fms antibody
M-CSF
url https://www.mdpi.com/1422-0067/21/17/6120
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