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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2020-08-01
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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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