Activated leukocyte cell adhesion molecule (ALCAM or CD166) modulates bone phenotype and hematopoiesis.
Year: 2015
Type: article
Abstract: Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166), is expressed on osteoblasts (OB) and hematopoietic stem cells (HSC) residing in the hematopoietic niche, and may have important regulatory roles in bone formation. Because HSC numbers are reduced 77% in CD166(-/-) mice, we hypothesized that changes in bone phenotype and consequently the endosteal niche may partially be responsible for this alteration. Therefore, we investigated bone phenotype and OB function in CD166(-/-) mice. Although osteoclastic measures were not affected by loss of CD166, CD166(-/-) mice exhibited a modest increase in trabecular bone fraction (42%), and increases in osteoid deposition (72%), OB number (60%), and bone formation rate (152%). Cortical bone geometry was altered in CD166(-/-) mice resulting in up to 81% and 49% increases in stiffness and ultimate force, respectively. CD166(-/-) OB displayed elevated alkaline phosphatase (ALP) activity and mineralization, and increased mRNA expression of Fra 1, ALP, and osteocalcin. Overall, CD166(-/-) mice displayed modestly elevated trabecular bone volume fraction with increased OB numbers and deposition of osteoid, and increased OB differentiation in vitro, possibly suggesting more mature OB are secreting more osteoid. This may explain the decline in HSC number in vivo because immature OB are mainly responsible for hematopoiesis enhancing activity.
Source: PubMed Central
Language: English
Topic: Bone Metabolism and Diseases
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: Regulating hematopoietic stem cells and hematopoiesis for clinical efficacy, Extrinsic Modulation of Hematopoietic Stem Cell Fate, Regulation of Osteoblast Function by Megakaryocytes: Key Signaling Proteins, Short-Term Training Program In Biomedical Sciences, Hematopoietic stem and progenitor cell regulation for enhanced clinical efficacy, Indiana University Melvin and Bren Simon Comprehensive Cancer Center Support Grant
OpenAlex ID: W2417552179
