title: Increased osteoclastogenesis in mice lacking the carcinoembryonic antigen-related cell adhesion molecule 1.
abstract: Alterations in bone remodeling are a major public health issue, as therapeutic options for widespread bone disorders such as osteoporosis and tumor-induced osteolysis are still limited. Therefore, a detailed understanding of the regulatory mechanism governing bone cell differentiation in health and disease are of utmost clinical importance. Here we report a novel function of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), a member of the immunoglobulin superfamily involved in inflammation and tumorigenesis, in the physiologic regulation of bone remodeling. Assessing the expression of all members of the murine Ceacam family in bone tissue and marrow, we found CEACAM1 and CEACAM10 to be differentially expressed in both bone-forming osteoblasts and bone-resorbing osteoclasts. While Ceacam10-deficient mice displayed no alteration in structural bone parameters, static histomorphometry demonstrated a reduced trabecular bone mass in mice lacking CEACAM1. Furthermore, cellular and dynamic histomorphometry revealed an increased osteoclast formation in Ceacam1-deficient mice, while osteoblast parameters and the bone formation rate remained unchanged. In line with these findings, we detected accelerated osteoclastogenesis in Ceacam1-deficient bone marrow cells, while osteoblast differentiation, as determined by mineralization and alkaline phosphatase assays, was not affected. Therefore, our results provide in vivo and in vitro evidence for a physiologic role of CEACAM1 in the regulation of osteoclastogenesis.
authors.affiliation: Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Heckt
authors.affiliation: Institute of Clinical Chemistry, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bickert
authors.affiliation: Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Jeschke
authors.affiliation: Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Seitz
authors.affiliation: Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Schulze
authors.affiliation: Cardiovascular Center Oberallgäu-Kempten, Im Stillen 3, Immenstadt 87509, Germany.
authors.forename: Wulf D
authors.initials: WD
authors.lastname: Ito
authors.affiliation: Tumor Immunology Laboratory, LIFE-Center, Klinikum Grosshadern, Ludwig-Maximilians-University Munich, Marchionistraße 15, Munich 81377, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Zimmermann
authors.affiliation: Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Amling
authors.affiliation: Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schinke
authors.affiliation: Institute of Clinical Chemistry, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany; Institute of Experimental Immunology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.
authors.forename: Andrea Kristina
authors.initials: AK
authors.lastname: Horst
authors.affiliation: Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Keller
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D001853:Bone Marrow / Q000378:metabolism; D016723:Bone Remodeling; D015815:Cell Adhesion Molecules / Q000172:deficiency* / Q000235:genetics; D002460:Cell Line; D005786:Gene Expression Regulation; D051379:Mice; D050778:NFATC Transcription Factors / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism; D010012:Osteogenesis; D010641:Phenotype
chemical_list: D015703:Antigens, CD; C069847:CD66 antigens; C470556:Ceacam10 protein, mouse; D015815:Cell Adhesion Molecules; D050778:NFATC Transcription Factors