Increased osteoclastogenesis in mice lacking the carcinoembryonic antigen-related cell adhesion molecule 1

PLoS One. 2014 Dec 9;9(12):e114360. doi: 10.1371/journal.pone.0114360. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Bone Marrow / metabolism
  • Bone Remodeling
  • Cell Adhesion Molecules / deficiency*
  • Cell Adhesion Molecules / genetics
  • Cell Line
  • Gene Expression Regulation
  • Mice
  • NFATC Transcription Factors / metabolism
  • Osteoblasts / cytology
  • Osteoblasts / metabolism
  • Osteoclasts / cytology*
  • Osteoclasts / metabolism
  • Osteogenesis
  • Phenotype

Substances

  • Antigens, CD
  • CD66 antigens
  • Ceacam10 protein, mouse
  • Cell Adhesion Molecules
  • NFATC Transcription Factors

Grants and funding

This work was supported by Deutsche Forschungsgemeinschaft SPP1468 IMMUNOBONE – Project SCHI 504/7-2 and IT13-3 - http://www.immunobone.de/ - TS WDI AKH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.