Osteoblast lineage-specific cell-surface antigen (A7) regulates osteoclast recruitment and calcification during bone remodeling

Tamer Badawy, Yukari Kyumoto, Norihisa Uehara, Jingqi Zhang, Soichiro Sonoda, Hidenobu Hiura, Takayoshi Yamaza, Akiko Kukita, Toshio Kukita

研究成果: ジャーナルへの寄稿記事

抄録

Bone remodeling is a continuous process characterized by highly coordinated cell-cell interactions in distinct multi-cellular units. Osteoclasts, which are specialized bone resorbing cells, play a central role in bone remodeling. Although the RANKL/RANK axis determines the gross number of osteoclasts present in bone tissue, detailed molecular events regulating bone remodeling related to osteoclast recruitment, initiation of bone remodeling, and coupling of bone resorption and bone formation are still ambiguous. We hypothesized that osteoblast-specific cell-surface molecules contribute to the molecular modulation of bone remodeling. Therefore, we searched for regulatory cell-surface molecules expressed on osteoblasts by use of B-cell hybridoma technology. We obtained a monoclonal antibody A7 (A7 MAb) highly specific to cells of osteoblast-lineage. Here we describe the expression pattern and possible role of A7 antigen specifically recognized by A7 MAb. In vitro, A7 antigen was expressed on cell-surface of osteoblasts and osteoblast-like bone marrow stromal cells. In vivo, A7 antigen was detected in a subset of bone surface osteoblasts and in osteocytes, with a typical cell membrane expression pattern. Tissue array analysis showed only a limited expression of A7 antigen in osteocytes close to the bone surface. Immunoblotting and immunoprecipitation analysis showed that A7 antigen is a lineage-specific cell-surface protein with an approximate molecular weight of 45 KDa. Cross-linking of cell-surface A7 antigen in cultures of osteoclastogenesis showed stimulation of osteoclast formation. Marked suppression of calcification in primary osteoblast cultures was observed when A7 antigen was cross-linked with anti-A7 antigen MAb, A7 MAb. These data suggest that A7 antigen regulates recruitment of osteoclasts and triggering of calcification. A7 antigen may be an important molecule involved in the precise regulation of bone remodeling.

元の言語英語
ページ(範囲)866-884
ページ数19
ジャーナルLaboratory Investigation
99
発行部数6
DOI
出版物ステータス出版済み - 6 1 2019

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Bone Remodeling
Osteoclasts
Surface Antigens
Osteoblasts
Antigens
Bone and Bones
Osteocytes
Osteogenesis
Tissue Array Analysis
Hybridomas
Cell Lineage
Bone Resorption
Mesenchymal Stromal Cells
Immunoprecipitation
Immunoblotting
Cell Communication
Membrane Proteins
B-Lymphocytes
Molecular Weight
Monoclonal Antibodies

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

これを引用

Osteoblast lineage-specific cell-surface antigen (A7) regulates osteoclast recruitment and calcification during bone remodeling. / Badawy, Tamer; Kyumoto, Yukari; Uehara, Norihisa; Zhang, Jingqi; Sonoda, Soichiro; Hiura, Hidenobu; Yamaza, Takayoshi; Kukita, Akiko; Kukita, Toshio.

:: Laboratory Investigation, 巻 99, 番号 6, 01.06.2019, p. 866-884.

研究成果: ジャーナルへの寄稿記事

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title = "Osteoblast lineage-specific cell-surface antigen (A7) regulates osteoclast recruitment and calcification during bone remodeling",
abstract = "Bone remodeling is a continuous process characterized by highly coordinated cell-cell interactions in distinct multi-cellular units. Osteoclasts, which are specialized bone resorbing cells, play a central role in bone remodeling. Although the RANKL/RANK axis determines the gross number of osteoclasts present in bone tissue, detailed molecular events regulating bone remodeling related to osteoclast recruitment, initiation of bone remodeling, and coupling of bone resorption and bone formation are still ambiguous. We hypothesized that osteoblast-specific cell-surface molecules contribute to the molecular modulation of bone remodeling. Therefore, we searched for regulatory cell-surface molecules expressed on osteoblasts by use of B-cell hybridoma technology. We obtained a monoclonal antibody A7 (A7 MAb) highly specific to cells of osteoblast-lineage. Here we describe the expression pattern and possible role of A7 antigen specifically recognized by A7 MAb. In vitro, A7 antigen was expressed on cell-surface of osteoblasts and osteoblast-like bone marrow stromal cells. In vivo, A7 antigen was detected in a subset of bone surface osteoblasts and in osteocytes, with a typical cell membrane expression pattern. Tissue array analysis showed only a limited expression of A7 antigen in osteocytes close to the bone surface. Immunoblotting and immunoprecipitation analysis showed that A7 antigen is a lineage-specific cell-surface protein with an approximate molecular weight of 45 KDa. Cross-linking of cell-surface A7 antigen in cultures of osteoclastogenesis showed stimulation of osteoclast formation. Marked suppression of calcification in primary osteoblast cultures was observed when A7 antigen was cross-linked with anti-A7 antigen MAb, A7 MAb. These data suggest that A7 antigen regulates recruitment of osteoclasts and triggering of calcification. A7 antigen may be an important molecule involved in the precise regulation of bone remodeling.",
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T1 - Osteoblast lineage-specific cell-surface antigen (A7) regulates osteoclast recruitment and calcification during bone remodeling

AU - Badawy, Tamer

AU - Kyumoto, Yukari

AU - Uehara, Norihisa

AU - Zhang, Jingqi

AU - Sonoda, Soichiro

AU - Hiura, Hidenobu

AU - Yamaza, Takayoshi

AU - Kukita, Akiko

AU - Kukita, Toshio

PY - 2019/6/1

Y1 - 2019/6/1

N2 - Bone remodeling is a continuous process characterized by highly coordinated cell-cell interactions in distinct multi-cellular units. Osteoclasts, which are specialized bone resorbing cells, play a central role in bone remodeling. Although the RANKL/RANK axis determines the gross number of osteoclasts present in bone tissue, detailed molecular events regulating bone remodeling related to osteoclast recruitment, initiation of bone remodeling, and coupling of bone resorption and bone formation are still ambiguous. We hypothesized that osteoblast-specific cell-surface molecules contribute to the molecular modulation of bone remodeling. Therefore, we searched for regulatory cell-surface molecules expressed on osteoblasts by use of B-cell hybridoma technology. We obtained a monoclonal antibody A7 (A7 MAb) highly specific to cells of osteoblast-lineage. Here we describe the expression pattern and possible role of A7 antigen specifically recognized by A7 MAb. In vitro, A7 antigen was expressed on cell-surface of osteoblasts and osteoblast-like bone marrow stromal cells. In vivo, A7 antigen was detected in a subset of bone surface osteoblasts and in osteocytes, with a typical cell membrane expression pattern. Tissue array analysis showed only a limited expression of A7 antigen in osteocytes close to the bone surface. Immunoblotting and immunoprecipitation analysis showed that A7 antigen is a lineage-specific cell-surface protein with an approximate molecular weight of 45 KDa. Cross-linking of cell-surface A7 antigen in cultures of osteoclastogenesis showed stimulation of osteoclast formation. Marked suppression of calcification in primary osteoblast cultures was observed when A7 antigen was cross-linked with anti-A7 antigen MAb, A7 MAb. These data suggest that A7 antigen regulates recruitment of osteoclasts and triggering of calcification. A7 antigen may be an important molecule involved in the precise regulation of bone remodeling.

AB - Bone remodeling is a continuous process characterized by highly coordinated cell-cell interactions in distinct multi-cellular units. Osteoclasts, which are specialized bone resorbing cells, play a central role in bone remodeling. Although the RANKL/RANK axis determines the gross number of osteoclasts present in bone tissue, detailed molecular events regulating bone remodeling related to osteoclast recruitment, initiation of bone remodeling, and coupling of bone resorption and bone formation are still ambiguous. We hypothesized that osteoblast-specific cell-surface molecules contribute to the molecular modulation of bone remodeling. Therefore, we searched for regulatory cell-surface molecules expressed on osteoblasts by use of B-cell hybridoma technology. We obtained a monoclonal antibody A7 (A7 MAb) highly specific to cells of osteoblast-lineage. Here we describe the expression pattern and possible role of A7 antigen specifically recognized by A7 MAb. In vitro, A7 antigen was expressed on cell-surface of osteoblasts and osteoblast-like bone marrow stromal cells. In vivo, A7 antigen was detected in a subset of bone surface osteoblasts and in osteocytes, with a typical cell membrane expression pattern. Tissue array analysis showed only a limited expression of A7 antigen in osteocytes close to the bone surface. Immunoblotting and immunoprecipitation analysis showed that A7 antigen is a lineage-specific cell-surface protein with an approximate molecular weight of 45 KDa. Cross-linking of cell-surface A7 antigen in cultures of osteoclastogenesis showed stimulation of osteoclast formation. Marked suppression of calcification in primary osteoblast cultures was observed when A7 antigen was cross-linked with anti-A7 antigen MAb, A7 MAb. These data suggest that A7 antigen regulates recruitment of osteoclasts and triggering of calcification. A7 antigen may be an important molecule involved in the precise regulation of bone remodeling.

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