PMID- 30423942 OWN - NLM STAT- MEDLINE DCOM- 20190228 LR - 20190228 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 19 IP - 11 DP - 2018 Nov 9 TI - Effects of a Pasty Bone Cement Containing Brain-Derived Neurotrophic Factor-Functionalized Mesoporous Bioactive Glass Particles on Metaphyseal Healing in a New Murine Osteoporotic Fracture Model. LID - 10.3390/ijms19113531 [doi] LID - 3531 AB - The development of new and better implant materials adapted to osteoporotic bone is still urgently required. Therefore, osteoporotic muscarinic acetylcholine receptor M3 (M3 mAChR) knockout (KO) and corresponding wild type (WT) mice underwent osteotomy in the distal femoral metaphysis. Fracture gaps were filled with a pasty alpha-tricalcium phosphate (alpha-TCP)-based hydroxyapatite (HA)-forming bone cement containing mesoporous bioactive CaP-SiO(2) glass particles (cement/MBG composite) with or without Brain-Derived Neurotrophic Factor (BDNF) and healing analyzed after 35 days. Histologically, bone formation was significantly increased in WT mice that received the BDNF-functionalized cement/MBG composite compared to control WT mice without BDNF. Cement/MBG composite without BDNF increased bone formation in M3 mAChR KO mice compared to equally treated WT mice. Mass spectrometric imaging showed that the BDNF-functionalized cement/MBG composite implanted in M3 mAChR KO mice was infiltrated by newly formed tissue. Leukocyte numbers were significantly lower in M3 mAChR KO mice treated with BDNF-functionalized cement/MBG composite compared to controls without BDNF. C-reactive protein (CRP) concentrations were significantly lower in M3 mAChR KO mice that received the cement/MBG composite without BDNF when compared to WT mice treated the same. Whereas alkaline phosphatase (ALP) concentrations in callus were significantly increased in M3 mAChR KO mice, ALP activity was significantly higher in WT mice. Due to a stronger effect of BDNF in non osteoporotic mice, higher BDNF concentrations might be needed for osteoporotic fracture healing. Nevertheless, the BDNF-functionalized cement/MBG composite promoted fracture healing in non osteoporotic bone. FAU - Kauschke, Vivien AU - Kauschke V AUID- ORCID: 0000-0002-4342-6875 AD - Experimental Trauma Surgery, Justus-Liebig-University Giessen, Aulweg 128, 35392 Giessen, Germany. Vivien.Kauschke@chiru.med.uni-giessen.de. FAU - Schneider, Maike AU - Schneider M AD - Experimental Trauma Surgery, Justus-Liebig-University Giessen, Aulweg 128, 35392 Giessen, Germany. maike.schneider33@gmx.de. FAU - Jauch, Annika AU - Jauch A AD - Experimental Trauma Surgery, Justus-Liebig-University Giessen, Aulweg 128, 35392 Giessen, Germany. annika@rebske.com. FAU - Schumacher, Matthias AU - Schumacher M AUID- ORCID: 0000-0001-7207-7355 AD - Centre for Translational Bone, Joint and Soft Tissue Research, Medical Faculty and University Hospital, Technische Universitat Dresden, Fetscherstrasse 74, 01307 Dresden, Germany. m.schumacher@maastrichtuniversity.nl. AD - Currently at MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, 6200 MD Maastricht, The Netherlands. m.schumacher@maastrichtuniversity.nl. FAU - Kampschulte, Marian AU - Kampschulte M AD - Department of Radiology, University Hospital of Giessen-Marburg, Campus Giessen Klinikstrasse 33, 35392 Giessen, Germany. Marian.Kampschulte@radiol.med.uni-giessen.de. FAU - Rohnke, Marcus AU - Rohnke M AUID- ORCID: 0000-0002-8867-950X AD - Institute of Physical Chemistry and Center for Materials Research, Justus-Liebig-University Giessen, Heinrich-Buff-Ring 17, 35392 Giessen, Germany. Marcus.Rohnke@phys.chemie.uni-giessen.de. FAU - Henss, Anja AU - Henss A AD - Institute of Physical Chemistry and Center for Materials Research, Justus-Liebig-University Giessen, Heinrich-Buff-Ring 17, 35392 Giessen, Germany. Anja.Henss@phys.Chemie.uni-giessen.de. FAU - Bamberg, Coralie AU - Bamberg C AD - Experimental Trauma Surgery, Justus-Liebig-University Giessen, Aulweg 128, 35392 Giessen, Germany. Coralie.E.Bamberg@med.uni-giessen.de. FAU - Trinkaus, Katja AU - Trinkaus K AD - Experimental Trauma Surgery, Justus-Liebig-University Giessen, Aulweg 128, 35392 Giessen, Germany. Katja.Trinkaus@chiru.med.uni-giessen.de. FAU - Gelinsky, Michael AU - Gelinsky M AUID- ORCID: 0000-0001-9075-5121 AD - Centre for Translational Bone, Joint and Soft Tissue Research, Medical Faculty and University Hospital, Technische Universitat Dresden, Fetscherstrasse 74, 01307 Dresden, Germany. michael.gelinsky@tu-dresden.de. FAU - Heiss, Christian AU - Heiss C AD - Experimental Trauma Surgery, Justus-Liebig-University Giessen, Aulweg 128, 35392 Giessen, Germany. Christian.Heiss@chiru.med.uni-giessen.de. AD - Department of Trauma, Hand and Reconstructive Surgery, University Hospital of Giessen-Marburg, Campus: Giessen, Rudolf-Buchheimstrasse 7, 35392 Giessen, Germany. Christian.Heiss@chiru.med.uni-giessen.de. FAU - Lips, Katrin Susanne AU - Lips KS AD - Experimental Trauma Surgery, Justus-Liebig-University Giessen, Aulweg 128, 35392 Giessen, Germany. Katrin.S.Lips@chiru.med.uni-giessen.de. LA - eng GR - SFB/TRR 79, projects B7, M2, M5 and Z3/Deutsche Forschungsgemeinschaft/ PT - Journal Article DEP - 20181109 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Bone Cements) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (RNA, Messenger) RN - 0 (Receptor, Muscarinic M3) RN - 9007-41-4 (C-Reactive Protein) RN - EC 3.1.3.1 (Alkaline Phosphatase) SB - IM MH - Alkaline Phosphatase/metabolism MH - Animals MH - Bone Cements/pharmacology/*therapeutic use MH - Bony Callus/drug effects/enzymology/pathology MH - Brain-Derived Neurotrophic Factor/pharmacology/*therapeutic use MH - C-Reactive Protein/metabolism MH - Disease Models, Animal MH - Female MH - Femur/diagnostic imaging/drug effects/*pathology MH - Fracture Healing/*drug effects MH - Glass/*chemistry MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Osteoporotic Fractures/blood/diagnostic imaging/*drug therapy/pathology MH - Porosity MH - RNA, Messenger/genetics/metabolism MH - Receptor, Muscarinic M3/metabolism MH - Spectrometry, X-Ray Emission MH - X-Ray Microtomography PMC - PMC6274902 OTO - NOTNLM OT - BDNF OT - mesoporous bioactive glass OT - metaphyseal fracture healing model OT - osteoporosis OT - alpha-TCP-based HA-forming bone cement COIS- The authors declare no conflict of interest. EDAT- 2018/11/15 06:00 MHDA- 2019/03/01 06:00 PMCR- 2018/11/01 CRDT- 2018/11/15 06:00 PHST- 2018/10/06 00:00 [received] PHST- 2018/10/29 00:00 [revised] PHST- 2018/11/05 00:00 [accepted] PHST- 2018/11/15 06:00 [entrez] PHST- 2018/11/15 06:00 [pubmed] PHST- 2019/03/01 06:00 [medline] PHST- 2018/11/01 00:00 [pmc-release] AID - ijms19113531 [pii] AID - ijms-19-03531 [pii] AID - 10.3390/ijms19113531 [doi] PST - epublish SO - Int J Mol Sci. 2018 Nov 9;19(11):3531. doi: 10.3390/ijms19113531.