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Temporal role of macrophages in cancellous bone healing
Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
2017 (English)In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 101, p. 129-133Article in journal (Refereed) Published
Abstract [en]

Macrophages are important phagocytosing and cytokine producing cells with effects on fracture healing. We used clodronate-containing liposomes to reduce the number of macrophages, in order to study their role in the early phases of cancellous bone healing. Holes were drilled bilaterally into the cancellous bone of the proximal metaphysis of the tibia of 60 mice. A screw was inserted in the hole in the right tibia. The day of surgery was day 0. Clodronate-containing liposomes were injected intraperitoneally as a single injection either day 4 or 1 (before surgery) or day 1 or 3 (after surgery). A control group underwent surgery as above, but received no clodronate. The mice were killed day 7. The mechanical quality of the new formed cancellous bone holding the screw was evaluated by a pull-out test. The contents of the drill hole in the left tibia was analyzed by microCT. Another set of 20 mice received a drill hole in the metaphysis of the right tibia, and were given either clodronate or saline injections days 3 and 2. The animals were killed day 1 and 3. Flow cytometry was used to analyze the composition of macrophage subpopulations in the regenerating tissue. Flow cytometry showed that clodronate injections day 3 and 2 led to a decrease in mature monocytes day 1 together with an increase in immature monocytes. On day 3 this effect had mostly disappeared, suggesting that the effect of the injections lasted 3 to 5 days. Mechanical testing revealed that the injections prior to surgery decreased the strength of the new formed bone, holding the screw, by about half. Bone density in the drill hole was similarly reduced. In contrast, the injections given day I and 3 had smaller and statistically insignificant effects. Since their depletion at later time points failed to produce a significant effect, it seems that the role of macrophages in cancellous bone is most crucial during the first two days after trauma. (C) 2017 Elsevier Inc. All rights reserved.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC , 2017. Vol. 101, p. 129-133
Keywords [en]
Macrophages; Bone healing; Flow cytometry; Cancellous; Metaphysis; Mechanical testing
National Category
Orthopaedics
Identifiers
URN: urn:nbn:se:liu:diva-139383DOI: 10.1016/j.bone.2017.04.004ISI: 000404319300016PubMedID: 28414141OAI: oai:DiVA.org:liu-139383DiVA, id: diva2:1129885
Note

Funding Agencies|Swedish Research Council [K2013-52X-02031-47-5]; Linkoping University; Ostergotland County Council [LiO-619221]; European Communitys Seventh Framework Program (FP7) [279239]

Available from: 2017-08-07 Created: 2017-08-07 Last updated: 2018-01-13

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Sandberg, OlofTätting, LoveBernhardsson, MagnusAspenberg, Per
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Division of Surgery, Orthopedics and OncologyFaculty of Medicine and Health SciencesDepartment of Orthopaedics in Linköping
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