title: Impact of acetylcholine and nicotine on human osteoclastogenesis in vitro.
abstract: Recent studies showed that the non-neuronal cholinergic system (NNCS) is taking part in bone metabolism. Most studies investigated its role in osteoblasts, but up to now, the involvement of the NNCS in human osteoclastogenesis remains relatively unclear. Thus, aim of the present study was to determine whether the application of acetylcholine (ACh, 10(−4) M), nicotine (10(−6) M), mineralized collagen membranes or brain derived neurotrophic factor (BDNF, 40 ng/mL) influences the mRNA regulation of molecular components of the NNCS and the neurotrophin family during osteoclastogenesis. Peripheral blood mononuclear cells (PBMCs) were isolated from the blood of young healthy donors (n = 8) and incubated with bone fragments and osteoclast differentiation media for 21 days. All the results are based on the measurement of RNA. Real-time RT-PCR analysis demonstrated a down-regulation of nicotinic acetylcholine receptor (nAChR) subunit α2 and muscarinic acetylcholine receptor (mAChR) M3by osteoclastogenesis while BDNF mRNA expression was not regulated. Application of ACh, nicotine, BDNF or collagen membranes did not affect osteoclastic differentiation.No regulation was detected for nAChR subunit α7, tropomyosin-related kinase receptor B (TrkB), and cholineacetyl transferase (ChAT). Taken together, we assume that the transcriptional level of osteoclastogenesis of healthy young humans is not regulated by BDNF, ACh, and nicotine. Thus, these drugs do not seem to worsen bone degradation and might therefore be suitable as modulators of bone substitution materials if having a positive effect on bone formation.
authors.affiliation: Laboratory for Experimental Trauma Surgery, Justus-Liebig University Giessen, Kerkraderstr. 9, 35394 Gießen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Ternes
authors.affiliation: Laboratory for Experimental Trauma Surgery, Justus-Liebig University Giessen, Kerkraderstr. 9, 35394 Gießen, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Trinkaus
authors.affiliation: Laboratory for Experimental Trauma Surgery, Justus-Liebig University Giessen, Kerkraderstr. 9, 35394 Gießen, Germany.
authors.forename: Ivonne
authors.initials: I
authors.lastname: Bergen
authors.affiliation: Centre for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus and Medical Faculty of Technische Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Knaack
authors.affiliation: Centre for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus and Medical Faculty of Technische Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Gelinsky
authors.affiliation: Department of Orthopedics and Trauma, Zentralklinik Bad Berka, Robert-Koch-Allee 9, 99437 Bad Berka, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Kilian
authors.affiliation: Laboratory for Experimental Trauma Surgery, Justus-Liebig University Giessen, Kerkraderstr. 9, 35394 Gießen, Germany; Department of Trauma Surgery Giessen, University Hospital of Giessen-Marburg, Campus Giessen, Rudolf-Buchheim-Str. 7, 35392 Giessen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Heiss
authors.affiliation: Laboratory for Experimental Trauma Surgery, Justus-Liebig University Giessen, Kerkraderstr. 9, 35394 Gießen, Germany. Electronic address: Katrin.S.Lips@chiru.med.uni-giessen.de.
authors.forename: Katrin Susanne
authors.initials: KS
authors.lastname: Lips
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D003094:Collagen; D005786:Gene Expression Regulation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D010010:Osteoclasts / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D009538:Nicotine; D003094:Collagen; D000109:Acetylcholine
keywords: Brain derived neurotrophic factor; Cathepsin-K; Nicotine; Osteoclast; Peripheral blood mononuclear cells; Real-time RT-PCR