Local administration of WP9QY (W9) peptide promotes bone formation in a rat femur delayed-union model
The WP9QY peptide (W9) consists of nine amino acids. It binds to RANKL and blocks RANKL-induced increases in bone resorption and osteoclastogenesis. W9 has a unique effect on the coupling mechanism between osteoclasts and osteoblasts, which promotes bone formation while working to suppress bone reso...
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| Veröffentlicht in: | Journal of bone and mineral metabolism 2018-07, Vol.36 (4), p.383-391 |
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| creator | Sawa, Mikiya Wakitani, Shigeyuki Kamei, Naosuke Kotaka, Shinji Adachi, Nobuo Ochi, Mitsuo |
| description | The WP9QY peptide (W9) consists of nine amino acids. It binds to RANKL and blocks RANKL-induced increases in bone resorption and osteoclastogenesis. W9 has a unique effect on the coupling mechanism between osteoclasts and osteoblasts, which promotes bone formation while working to suppress bone resorption. In this study, with the aim of clinical application of W9 for fracture treatment, we aimed to clarify the bone repair-promoting effect of W9 when administered locally to a rat femur model of delayed union. Using Sprague–Dawley rats, a model of delayed union was created in the right femur by cauterizing the periosteum. Injection of W9 (1 mg in 100 μl) or phosphate-buffered saline (PBS) (100 μl) at the fracture site was performed at the operation and every week thereafter until death (sacrifice). The bone union rate was 14% in the PBS group and 57% in the W9 group at 8 weeks postoperatively. The X-ray score of the W9 group was significantly higher than that of the PBS group at 8 weeks postoperatively. When bone morphometry was analyzed by micro-computed tomography (CT), total callus volume (TV) and mineralized callus bone volume (BV) were measured. TV showed no significant difference between the two groups, but BV/TV was significantly higher in the W9 group. This finding suggests that local administration of W9 can promote bone maturation from callus and can be considered to contribute to fracture healing. These results reveal that W9 has an effect on fractures of promoting healing and could be applied as a fracture treatment. |
| doi_str_mv | 10.1007/s00774-017-0852-5 |
| format | Article |
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It binds to RANKL and blocks RANKL-induced increases in bone resorption and osteoclastogenesis. W9 has a unique effect on the coupling mechanism between osteoclasts and osteoblasts, which promotes bone formation while working to suppress bone resorption. In this study, with the aim of clinical application of W9 for fracture treatment, we aimed to clarify the bone repair-promoting effect of W9 when administered locally to a rat femur model of delayed union. Using Sprague–Dawley rats, a model of delayed union was created in the right femur by cauterizing the periosteum. Injection of W9 (1 mg in 100 μl) or phosphate-buffered saline (PBS) (100 μl) at the fracture site was performed at the operation and every week thereafter until death (sacrifice). The bone union rate was 14% in the PBS group and 57% in the W9 group at 8 weeks postoperatively. The X-ray score of the W9 group was significantly higher than that of the PBS group at 8 weeks postoperatively. When bone morphometry was analyzed by micro-computed tomography (CT), total callus volume (TV) and mineralized callus bone volume (BV) were measured. TV showed no significant difference between the two groups, but BV/TV was significantly higher in the W9 group. This finding suggests that local administration of W9 can promote bone maturation from callus and can be considered to contribute to fracture healing. These results reveal that W9 has an effect on fractures of promoting healing and could be applied as a fracture treatment.</description><identifier>ISSN: 0914-8779</identifier><identifier>EISSN: 1435-5604</identifier><identifier>DOI: 10.1007/s00774-017-0852-5</identifier><identifier>PMID: 28660377</identifier><language>eng</language><publisher>Tokyo: Springer Japan</publisher><subject>Animals ; Bone growth ; Bone healing ; Bone resorption ; Bony Callus - drug effects ; Bony Callus - pathology ; Calcification, Physiologic ; Callus ; Cell Count ; Computed tomography ; Disease Models, Animal ; Femoral Fractures - diagnostic imaging ; Femoral Fractures - drug therapy ; Femur ; Femur - diagnostic imaging ; Femur - drug effects ; Femur - pathology ; Fracture Healing - drug effects ; Fractures ; Gene Expression Regulation - drug effects ; Male ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Morphometry ; Original Article ; Orthopedics ; Osteoblasts ; Osteoblasts - drug effects ; Osteoblasts - metabolism ; Osteoclastogenesis ; Osteoclasts ; Osteogenesis ; Osteogenesis - drug effects ; Osteogenesis - genetics ; Peptides, Cyclic - administration & dosage ; Peptides, Cyclic - pharmacology ; Peptides, Cyclic - therapeutic use ; Periosteum ; Rats, Sprague-Dawley ; Tartrate-Resistant Acid Phosphatase - metabolism ; TRANCE protein ; X-Ray Microtomography</subject><ispartof>Journal of bone and mineral metabolism, 2018-07, Vol.36 (4), p.383-391</ispartof><rights>The Japanese Society for Bone and Mineral Research and Springer Japan KK 2017</rights><rights>Journal of Bone and Mineral Metabolism is a copyright of Springer, (2017). 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It binds to RANKL and blocks RANKL-induced increases in bone resorption and osteoclastogenesis. W9 has a unique effect on the coupling mechanism between osteoclasts and osteoblasts, which promotes bone formation while working to suppress bone resorption. In this study, with the aim of clinical application of W9 for fracture treatment, we aimed to clarify the bone repair-promoting effect of W9 when administered locally to a rat femur model of delayed union. Using Sprague–Dawley rats, a model of delayed union was created in the right femur by cauterizing the periosteum. Injection of W9 (1 mg in 100 μl) or phosphate-buffered saline (PBS) (100 μl) at the fracture site was performed at the operation and every week thereafter until death (sacrifice). The bone union rate was 14% in the PBS group and 57% in the W9 group at 8 weeks postoperatively. The X-ray score of the W9 group was significantly higher than that of the PBS group at 8 weeks postoperatively. When bone morphometry was analyzed by micro-computed tomography (CT), total callus volume (TV) and mineralized callus bone volume (BV) were measured. TV showed no significant difference between the two groups, but BV/TV was significantly higher in the W9 group. This finding suggests that local administration of W9 can promote bone maturation from callus and can be considered to contribute to fracture healing. These results reveal that W9 has an effect on fractures of promoting healing and could be applied as a fracture treatment.</description><subject>Animals</subject><subject>Bone growth</subject><subject>Bone healing</subject><subject>Bone resorption</subject><subject>Bony Callus - drug effects</subject><subject>Bony Callus - pathology</subject><subject>Calcification, Physiologic</subject><subject>Callus</subject><subject>Cell Count</subject><subject>Computed tomography</subject><subject>Disease Models, Animal</subject><subject>Femoral Fractures - diagnostic imaging</subject><subject>Femoral Fractures - drug therapy</subject><subject>Femur</subject><subject>Femur - diagnostic imaging</subject><subject>Femur - drug effects</subject><subject>Femur - pathology</subject><subject>Fracture Healing - drug effects</subject><subject>Fractures</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic Diseases</subject><subject>Morphometry</subject><subject>Original Article</subject><subject>Orthopedics</subject><subject>Osteoblasts</subject><subject>Osteoblasts - drug effects</subject><subject>Osteoblasts - metabolism</subject><subject>Osteoclastogenesis</subject><subject>Osteoclasts</subject><subject>Osteogenesis</subject><subject>Osteogenesis - drug effects</subject><subject>Osteogenesis - genetics</subject><subject>Peptides, Cyclic - administration & dosage</subject><subject>Peptides, Cyclic - pharmacology</subject><subject>Peptides, Cyclic - therapeutic use</subject><subject>Periosteum</subject><subject>Rats, Sprague-Dawley</subject><subject>Tartrate-Resistant Acid Phosphatase - metabolism</subject><subject>TRANCE protein</subject><subject>X-Ray Microtomography</subject><issn>0914-8779</issn><issn>1435-5604</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1kUtr3DAUhUVpaCaPH9BNEXSTLJReydZrWUKbBAaSQMOQlVDk6-JgW1PJXuTfR4OnLQSykRD3O0eXcwj5zOGCA-hvuRy6ZsA1AyMFkx_IiteVZFJB_ZGswPKaGa3tITnK-RkKKDX_RA6FUQoqrVcE1zH4nvpm6MYuT8lPXRxpbOnmzt4_0rONPadb3E5dg3Sb4hAnzPQpjkjbmIaF7kbqaVHSFoc50QZ7_4INm8fdcIjlfUIOWt9nPN3fx-Th549fl9dsfXt1c_l9zYI0dmJGoEdZIaiqDtwYUynLAYNBEC03yhqvUEBrROut5KCCDdLqxqugvNemOiZni29Z9c-MeXJDlwP2vR8xztnxEoiRAKIq6Nc36HOc01i2cwJUCUooqQvFFyqkmHPC1m1TN_j04ji4XQdu6cCVaN2uAyeL5sveeX4asPmn-Bt6AcQC5DIaf2P6__X7rq84po_Y</recordid><startdate>20180701</startdate><enddate>20180701</enddate><creator>Sawa, Mikiya</creator><creator>Wakitani, Shigeyuki</creator><creator>Kamei, Naosuke</creator><creator>Kotaka, Shinji</creator><creator>Adachi, Nobuo</creator><creator>Ochi, Mitsuo</creator><general>Springer Japan</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20180701</creationdate><title>Local administration of WP9QY (W9) peptide promotes bone formation in a rat femur delayed-union model</title><author>Sawa, Mikiya ; Wakitani, Shigeyuki ; Kamei, Naosuke ; Kotaka, Shinji ; Adachi, Nobuo ; Ochi, Mitsuo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c589t-82eae53e0634c188836910ec8e02f18698a6e20f82fa95106c9c597da6c6aa783</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Bone growth</topic><topic>Bone healing</topic><topic>Bone resorption</topic><topic>Bony Callus - drug effects</topic><topic>Bony Callus - pathology</topic><topic>Calcification, Physiologic</topic><topic>Callus</topic><topic>Cell Count</topic><topic>Computed tomography</topic><topic>Disease Models, Animal</topic><topic>Femoral Fractures - diagnostic imaging</topic><topic>Femoral Fractures - drug therapy</topic><topic>Femur</topic><topic>Femur - diagnostic imaging</topic><topic>Femur - drug effects</topic><topic>Femur - pathology</topic><topic>Fracture Healing - drug effects</topic><topic>Fractures</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolic Diseases</topic><topic>Morphometry</topic><topic>Original Article</topic><topic>Orthopedics</topic><topic>Osteoblasts</topic><topic>Osteoblasts - drug effects</topic><topic>Osteoblasts - metabolism</topic><topic>Osteoclastogenesis</topic><topic>Osteoclasts</topic><topic>Osteogenesis</topic><topic>Osteogenesis - drug effects</topic><topic>Osteogenesis - genetics</topic><topic>Peptides, Cyclic - administration & dosage</topic><topic>Peptides, Cyclic - pharmacology</topic><topic>Peptides, Cyclic - therapeutic use</topic><topic>Periosteum</topic><topic>Rats, Sprague-Dawley</topic><topic>Tartrate-Resistant Acid Phosphatase - metabolism</topic><topic>TRANCE protein</topic><topic>X-Ray Microtomography</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sawa, Mikiya</creatorcontrib><creatorcontrib>Wakitani, Shigeyuki</creatorcontrib><creatorcontrib>Kamei, Naosuke</creatorcontrib><creatorcontrib>Kotaka, Shinji</creatorcontrib><creatorcontrib>Adachi, Nobuo</creatorcontrib><creatorcontrib>Ochi, Mitsuo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of bone and mineral metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sawa, Mikiya</au><au>Wakitani, Shigeyuki</au><au>Kamei, Naosuke</au><au>Kotaka, Shinji</au><au>Adachi, Nobuo</au><au>Ochi, Mitsuo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Local administration of WP9QY (W9) peptide promotes bone formation in a rat femur delayed-union model</atitle><jtitle>Journal of bone and mineral metabolism</jtitle><stitle>J Bone Miner Metab</stitle><addtitle>J Bone Miner Metab</addtitle><date>2018-07-01</date><risdate>2018</risdate><volume>36</volume><issue>4</issue><spage>383</spage><epage>391</epage><pages>383-391</pages><issn>0914-8779</issn><eissn>1435-5604</eissn><abstract>The WP9QY peptide (W9) consists of nine amino acids. It binds to RANKL and blocks RANKL-induced increases in bone resorption and osteoclastogenesis. W9 has a unique effect on the coupling mechanism between osteoclasts and osteoblasts, which promotes bone formation while working to suppress bone resorption. In this study, with the aim of clinical application of W9 for fracture treatment, we aimed to clarify the bone repair-promoting effect of W9 when administered locally to a rat femur model of delayed union. Using Sprague–Dawley rats, a model of delayed union was created in the right femur by cauterizing the periosteum. Injection of W9 (1 mg in 100 μl) or phosphate-buffered saline (PBS) (100 μl) at the fracture site was performed at the operation and every week thereafter until death (sacrifice). The bone union rate was 14% in the PBS group and 57% in the W9 group at 8 weeks postoperatively. The X-ray score of the W9 group was significantly higher than that of the PBS group at 8 weeks postoperatively. When bone morphometry was analyzed by micro-computed tomography (CT), total callus volume (TV) and mineralized callus bone volume (BV) were measured. TV showed no significant difference between the two groups, but BV/TV was significantly higher in the W9 group. This finding suggests that local administration of W9 can promote bone maturation from callus and can be considered to contribute to fracture healing. These results reveal that W9 has an effect on fractures of promoting healing and could be applied as a fracture treatment.</abstract><cop>Tokyo</cop><pub>Springer Japan</pub><pmid>28660377</pmid><doi>10.1007/s00774-017-0852-5</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Bone growth Bone healing Bone resorption Bony Callus - drug effects Bony Callus - pathology Calcification, Physiologic Callus Cell Count Computed tomography Disease Models, Animal Femoral Fractures - diagnostic imaging Femoral Fractures - drug therapy Femur Femur - diagnostic imaging Femur - drug effects Femur - pathology Fracture Healing - drug effects Fractures Gene Expression Regulation - drug effects Male Medicine Medicine & Public Health Metabolic Diseases Morphometry Original Article Orthopedics Osteoblasts Osteoblasts - drug effects Osteoblasts - metabolism Osteoclastogenesis Osteoclasts Osteogenesis Osteogenesis - drug effects Osteogenesis - genetics Peptides, Cyclic - administration & dosage Peptides, Cyclic - pharmacology Peptides, Cyclic - therapeutic use Periosteum Rats, Sprague-Dawley Tartrate-Resistant Acid Phosphatase - metabolism TRANCE protein X-Ray Microtomography |
| title | Local administration of WP9QY (W9) peptide promotes bone formation in a rat femur delayed-union model |
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