Regulation of Osteoblast Levels During Bone Healing

OBJECTIVE:To confirm the occurrence of programmed cell death of osteoblasts during bone healing and to evaluate the role of interleukin-1β (IL-1β) in regulating osteoblast concentration. STUDY DESIGN:Electron microscopic study of the response of rats to a controlled bone injury, and a randomized con...

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Veröffentlicht in:Journal of orthopaedic trauma 1999-06, Vol.13 (5), p.356-362
Hauptverfasser: Olmedo, Margaret L, Landry, Patricia S, Sadasivan, Kalia K, Albright, James A, Meek, William D, Routh, Robert, Marino, Andrew A
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container_end_page 362
container_issue 5
container_start_page 356
container_title Journal of orthopaedic trauma
container_volume 13
creator Olmedo, Margaret L
Landry, Patricia S
Sadasivan, Kalia K
Albright, James A
Meek, William D
Routh, Robert
Marino, Andrew A
description OBJECTIVE:To confirm the occurrence of programmed cell death of osteoblasts during bone healing and to evaluate the role of interleukin-1β (IL-1β) in regulating osteoblast concentration. STUDY DESIGN:Electron microscopic study of the response of rats to a controlled bone injury, and a randomized controlled study of the effect of IL-1β administered continuously for three days. METHODS:A standardized defect (1.1 millimeter in diameter, 0.5 millimeter deep) was created unilaterally on the anteromedial surface of the tibia. In some animals, the injury site was recovered five days after operation and processed for ultrastructural evaluation of osteoblasts in the callus. In another group, IL-1β was delivered to the bone defect using micro-osmotic pumps (0.5 nanograms/hour); control rats received vehicle only. The bones were recovered one to fourteen days after injury, and concentrations of proliferating cells, osteoblasts, and apoptotic bodies were determined. The amount of callus that formed in the defect was measured. RESULTS:Osteoblasts in the callus exhibited ultrastructural changes characteristic of cells undergoing apoptosis, including condensation of chromatin, membrane blebbing, formation of apoptotic bodies, and phagocytosis by nearby osteoblasts. Addition of IL-1β significantly increased the number of osteoblasts at the injury site and significantly decreased the number of apoptotic bodies in relation to the number of osteoblasts. The amount of callus in the bone defect was not affected by IL-1β treatment. CONCLUSION:The role of programmed cell death of osteoblasts as a normal concomitant of bone healing was confirmed. Evidence was found suggesting that IL-1β mediated the appearance and disappearance of osteoblasts, possibly by affecting the rates of differentiation and apoptosis, respectively. Understanding these mechanisms conceivably could lead to the ability to control osteoblast levels at an injury site.
doi_str_mv 10.1097/00005131-199906000-00006
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STUDY DESIGN:Electron microscopic study of the response of rats to a controlled bone injury, and a randomized controlled study of the effect of IL-1β administered continuously for three days. METHODS:A standardized defect (1.1 millimeter in diameter, 0.5 millimeter deep) was created unilaterally on the anteromedial surface of the tibia. In some animals, the injury site was recovered five days after operation and processed for ultrastructural evaluation of osteoblasts in the callus. In another group, IL-1β was delivered to the bone defect using micro-osmotic pumps (0.5 nanograms/hour); control rats received vehicle only. The bones were recovered one to fourteen days after injury, and concentrations of proliferating cells, osteoblasts, and apoptotic bodies were determined. The amount of callus that formed in the defect was measured. RESULTS:Osteoblasts in the callus exhibited ultrastructural changes characteristic of cells undergoing apoptosis, including condensation of chromatin, membrane blebbing, formation of apoptotic bodies, and phagocytosis by nearby osteoblasts. Addition of IL-1β significantly increased the number of osteoblasts at the injury site and significantly decreased the number of apoptotic bodies in relation to the number of osteoblasts. The amount of callus in the bone defect was not affected by IL-1β treatment. CONCLUSION:The role of programmed cell death of osteoblasts as a normal concomitant of bone healing was confirmed. Evidence was found suggesting that IL-1β mediated the appearance and disappearance of osteoblasts, possibly by affecting the rates of differentiation and apoptosis, respectively. Understanding these mechanisms conceivably could lead to the ability to control osteoblast levels at an injury site.</description><identifier>ISSN: 0890-5339</identifier><identifier>EISSN: 1531-2291</identifier><identifier>DOI: 10.1097/00005131-199906000-00006</identifier><identifier>PMID: 10406703</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams &amp; Wilkins, Inc</publisher><subject>Animals ; Apoptosis ; Biological and medical sciences ; Bone and Bones - injuries ; Bone and Bones - pathology ; Degeneration. Regeneration. Wound healing. Graft ; Disease Models, Animal ; Fracture Healing - physiology ; Fractures, Bone - pathology ; Fundamental and applied biological sciences. Psychology ; Interleukin-1 - analysis ; Interleukin-1 - biosynthesis ; Male ; Osteoblasts - pathology ; Random Allocation ; Rats ; Rats, Inbred F344 ; Reference Values ; Sensitivity and Specificity ; Statistics, Nonparametric ; Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><ispartof>Journal of orthopaedic trauma, 1999-06, Vol.13 (5), p.356-362</ispartof><rights>1999 Lippincott Williams &amp; Wilkins, Inc.</rights><rights>1999 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4146-17a90ef0d42739791d01f9e4f8b2a89e1fbd1b7559f45743e2260eb0bcb45e5d3</citedby><cites>FETCH-LOGICAL-c4146-17a90ef0d42739791d01f9e4f8b2a89e1fbd1b7559f45743e2260eb0bcb45e5d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=1864937$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10406703$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Olmedo, Margaret L</creatorcontrib><creatorcontrib>Landry, Patricia S</creatorcontrib><creatorcontrib>Sadasivan, Kalia K</creatorcontrib><creatorcontrib>Albright, James A</creatorcontrib><creatorcontrib>Meek, William D</creatorcontrib><creatorcontrib>Routh, Robert</creatorcontrib><creatorcontrib>Marino, Andrew A</creatorcontrib><title>Regulation of Osteoblast Levels During Bone Healing</title><title>Journal of orthopaedic trauma</title><addtitle>J Orthop Trauma</addtitle><description>OBJECTIVE:To confirm the occurrence of programmed cell death of osteoblasts during bone healing and to evaluate the role of interleukin-1β (IL-1β) in regulating osteoblast concentration. STUDY DESIGN:Electron microscopic study of the response of rats to a controlled bone injury, and a randomized controlled study of the effect of IL-1β administered continuously for three days. METHODS:A standardized defect (1.1 millimeter in diameter, 0.5 millimeter deep) was created unilaterally on the anteromedial surface of the tibia. In some animals, the injury site was recovered five days after operation and processed for ultrastructural evaluation of osteoblasts in the callus. In another group, IL-1β was delivered to the bone defect using micro-osmotic pumps (0.5 nanograms/hour); control rats received vehicle only. The bones were recovered one to fourteen days after injury, and concentrations of proliferating cells, osteoblasts, and apoptotic bodies were determined. The amount of callus that formed in the defect was measured. RESULTS:Osteoblasts in the callus exhibited ultrastructural changes characteristic of cells undergoing apoptosis, including condensation of chromatin, membrane blebbing, formation of apoptotic bodies, and phagocytosis by nearby osteoblasts. Addition of IL-1β significantly increased the number of osteoblasts at the injury site and significantly decreased the number of apoptotic bodies in relation to the number of osteoblasts. The amount of callus in the bone defect was not affected by IL-1β treatment. CONCLUSION:The role of programmed cell death of osteoblasts as a normal concomitant of bone healing was confirmed. Evidence was found suggesting that IL-1β mediated the appearance and disappearance of osteoblasts, possibly by affecting the rates of differentiation and apoptosis, respectively. Understanding these mechanisms conceivably could lead to the ability to control osteoblast levels at an injury site.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Biological and medical sciences</subject><subject>Bone and Bones - injuries</subject><subject>Bone and Bones - pathology</subject><subject>Degeneration. Regeneration. Wound healing. Graft</subject><subject>Disease Models, Animal</subject><subject>Fracture Healing - physiology</subject><subject>Fractures, Bone - pathology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Interleukin-1 - analysis</subject><subject>Interleukin-1 - biosynthesis</subject><subject>Male</subject><subject>Osteoblasts - pathology</subject><subject>Random Allocation</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Reference Values</subject><subject>Sensitivity and Specificity</subject><subject>Statistics, Nonparametric</subject><subject>Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><issn>0890-5339</issn><issn>1531-2291</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kclOwzAQhi0EoqXwCigHxC0wXrL4CGUpUqVKCM6Wk4zbgJsUO6Hi7XFpWS7MxZpf38xInwmJKFxQkNklhEoopzGVUkIaungTpXtkSJMQMybpPhlCLiFOOJcDcuT9SyByYOyQDCgISDPgQ8Ifcd5b3dVtE7UmmvkO28Jq30VTfEfro5ve1c08um4bjCaobWiOyYHR1uPJ7h2R57vbp_Ekns7uH8ZX07gUVKQxzbQENFAJlnGZSVoBNRKFyQumc4nUFBUtsiSRRiSZ4MhYClhAURYiwaTiI3K-3bty7VuPvlPL2pdorW6w7b1KZS4FAxrAfAuWrvXeoVErVy-1-1AU1EaY-hamfoR9RWkYPd3d6IslVn8Gt4YCcLYDtC-1NU43Ze1_uTwVkmcBE1ts3doOnX-1_RqdWgRj3UL991_8Ey-mgHA</recordid><startdate>199906</startdate><enddate>199906</enddate><creator>Olmedo, Margaret L</creator><creator>Landry, Patricia S</creator><creator>Sadasivan, Kalia K</creator><creator>Albright, James A</creator><creator>Meek, William D</creator><creator>Routh, Robert</creator><creator>Marino, Andrew A</creator><general>Lippincott Williams &amp; Wilkins, Inc</general><general>Lippincott Williams &amp; Wilkins</general><scope>IQODW</scope><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>7X8</scope></search><sort><creationdate>199906</creationdate><title>Regulation of Osteoblast Levels During Bone Healing</title><author>Olmedo, Margaret L ; Landry, Patricia S ; Sadasivan, Kalia K ; Albright, James A ; Meek, William D ; Routh, Robert ; Marino, Andrew A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4146-17a90ef0d42739791d01f9e4f8b2a89e1fbd1b7559f45743e2260eb0bcb45e5d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>Biological and medical sciences</topic><topic>Bone and Bones - injuries</topic><topic>Bone and Bones - pathology</topic><topic>Degeneration. Regeneration. Wound healing. Graft</topic><topic>Disease Models, Animal</topic><topic>Fracture Healing - physiology</topic><topic>Fractures, Bone - pathology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Interleukin-1 - analysis</topic><topic>Interleukin-1 - biosynthesis</topic><topic>Male</topic><topic>Osteoblasts - pathology</topic><topic>Random Allocation</topic><topic>Rats</topic><topic>Rats, Inbred F344</topic><topic>Reference Values</topic><topic>Sensitivity and Specificity</topic><topic>Statistics, Nonparametric</topic><topic>Vertebrates: anatomy and physiology, studies on body, several organs or systems</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Olmedo, Margaret L</creatorcontrib><creatorcontrib>Landry, Patricia S</creatorcontrib><creatorcontrib>Sadasivan, Kalia K</creatorcontrib><creatorcontrib>Albright, James A</creatorcontrib><creatorcontrib>Meek, William D</creatorcontrib><creatorcontrib>Routh, Robert</creatorcontrib><creatorcontrib>Marino, Andrew A</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of orthopaedic trauma</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Olmedo, Margaret L</au><au>Landry, Patricia S</au><au>Sadasivan, Kalia K</au><au>Albright, James A</au><au>Meek, William D</au><au>Routh, Robert</au><au>Marino, Andrew A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regulation of Osteoblast Levels During Bone Healing</atitle><jtitle>Journal of orthopaedic trauma</jtitle><addtitle>J Orthop Trauma</addtitle><date>1999-06</date><risdate>1999</risdate><volume>13</volume><issue>5</issue><spage>356</spage><epage>362</epage><pages>356-362</pages><issn>0890-5339</issn><eissn>1531-2291</eissn><abstract>OBJECTIVE:To confirm the occurrence of programmed cell death of osteoblasts during bone healing and to evaluate the role of interleukin-1β (IL-1β) in regulating osteoblast concentration. STUDY DESIGN:Electron microscopic study of the response of rats to a controlled bone injury, and a randomized controlled study of the effect of IL-1β administered continuously for three days. METHODS:A standardized defect (1.1 millimeter in diameter, 0.5 millimeter deep) was created unilaterally on the anteromedial surface of the tibia. In some animals, the injury site was recovered five days after operation and processed for ultrastructural evaluation of osteoblasts in the callus. In another group, IL-1β was delivered to the bone defect using micro-osmotic pumps (0.5 nanograms/hour); control rats received vehicle only. The bones were recovered one to fourteen days after injury, and concentrations of proliferating cells, osteoblasts, and apoptotic bodies were determined. The amount of callus that formed in the defect was measured. RESULTS:Osteoblasts in the callus exhibited ultrastructural changes characteristic of cells undergoing apoptosis, including condensation of chromatin, membrane blebbing, formation of apoptotic bodies, and phagocytosis by nearby osteoblasts. Addition of IL-1β significantly increased the number of osteoblasts at the injury site and significantly decreased the number of apoptotic bodies in relation to the number of osteoblasts. The amount of callus in the bone defect was not affected by IL-1β treatment. CONCLUSION:The role of programmed cell death of osteoblasts as a normal concomitant of bone healing was confirmed. Evidence was found suggesting that IL-1β mediated the appearance and disappearance of osteoblasts, possibly by affecting the rates of differentiation and apoptosis, respectively. Understanding these mechanisms conceivably could lead to the ability to control osteoblast levels at an injury site.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams &amp; Wilkins, Inc</pub><pmid>10406703</pmid><doi>10.1097/00005131-199906000-00006</doi><tpages>7</tpages></addata></record>
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subjects Animals
Apoptosis
Biological and medical sciences
Bone and Bones - injuries
Bone and Bones - pathology
Degeneration. Regeneration. Wound healing. Graft
Disease Models, Animal
Fracture Healing - physiology
Fractures, Bone - pathology
Fundamental and applied biological sciences. Psychology
Interleukin-1 - analysis
Interleukin-1 - biosynthesis
Male
Osteoblasts - pathology
Random Allocation
Rats
Rats, Inbred F344
Reference Values
Sensitivity and Specificity
Statistics, Nonparametric
Vertebrates: anatomy and physiology, studies on body, several organs or systems
title Regulation of Osteoblast Levels During Bone Healing
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