title: Regulation of acetylcholine receptors during differentiation of bone mesenchymal stem cells harvested from human reaming debris.
abstract: Acetylcholine (ACh) is an important signaling molecule in non-neuronal systems where it is involved in regulation of viability, proliferation, differentiation and migration of mesenchymal stem cells (MSC) that are capable to differentiate into osteoblasts, chondrocytes and adipocytes. Patients with the systemic disease osteoporosis show altered MSC properties, reduced bone formation and mineral density followed by increased bone fragility and high fracture incidence. Here we asked whether nicotinic and muscarinic acetylcholine receptors (AChR) are expressed in osteoblasts, adipocytes and chondrocytes differentiated from bone MSC extracted from human reaming debris (RDMSC) that was harvested during surgery of long bone diaphyseal fractures. Using RT-PCR, AChR were detected in RDMSC, osteoblasts, chondrocytes and adipocytes of male and female bone-healthy and of female osteoporotic donors. An up-regulation in multiplicity and occurrence of AChR subtypes was found in female compared to male donors and in osteoblast of male donors compared to adipocytes. Real-time RT-PCR analysis resulted in a significant increase in relative expression of nAChR α9 in chondrocytes compared to adipocytes of healthy female donors. The nAChR subunit α10 was significantly up-regulated in osteoblasts of healthy compared to osteoporotic donors as well as the mAChR M5 that is additionally decreased in osteoporotic osteoblasts compared to MSC and chondrocytes of osteoporotic donors. In summary, the gene expression of AChR during differentiation of RDMSC and its regulation in cells of osteoporotic donors lead to the assumption that AChR signaling is involved in bone formation and might be utilized to stimulate bone remodeling processes.
authors.affiliation: Laboratory for Experimental Trauma Surgery, Justus-Liebig University, Kerkraderstr. 9, 35394 Giessen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Zablotni
authors.affiliation: Laboratory for Experimental Trauma Surgery, Justus-Liebig University, Kerkraderstr. 9, 35394 Giessen, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Dakischew
authors.affiliation: Laboratory for Experimental Trauma Surgery, Justus-Liebig University, Kerkraderstr. 9, 35394 Giessen, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Trinkaus
authors.affiliation: Laboratory for Experimental Trauma Surgery, Justus-Liebig University, Kerkraderstr. 9, 35394 Giessen, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Hartmann
authors.affiliation: Department of Trauma Surgery Giessen, University Hospital of Giessen-Marburg, Campus Giessen, Rudolf-Buchheim-Str. 7, 35392 Giessen, Germany.
authors.forename: Gabor
authors.initials: G
authors.lastname: Szalay
authors.affiliation: Laboratory for Experimental Trauma Surgery, Justus-Liebig University, 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, 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: D017667:Adipocytes / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D008875:Middle Aged; D010006:Osteoblasts / Q000378:metabolism; D010024:Osteoporosis / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011976:Receptors, Muscarinic / Q000235:genetics / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic
keywords: Adipocyte; Chondrocyte; Differentiation; Mesenchymal stem cells; Muscarinic receptor; Nicotinic receptor; Osteoblast