title: Hypoxic osteocytes recruit human MSCs through an OPN/CD44-mediated pathway.
abstract: Little is known about the role or identity of signaling molecules released by osteocytes to recruit MSCs to areas of matrix damage. Vascular disruption at fracture sites results in hypoxia which is known to up-regulate genes involved in cell migration including osteopontin (OPN). We examined the effect of conditioned media from hypoxic osteocytes on MSC migration. Hypoxic osteocyte media significantly increased MSC migration and expression of OPN was significantly increased in hypoxic osteocytes. OPN and CD44 neutralizing antibodies significantly reduced MSC migration. Further, recombinant OPN significantly increased MSC migration in a dose-dependent manner. Our data support the hypothesis that hypoxia at a fracture site stimulates the release of chemotactic factors, such as OPN, from osteocytes, that induce MSC migration to aid in fracture repair. To our knowledge, these are the first data to suggest a role for osteocytes and OPN in the recruitment of MSCs to aid in fracture repair.
authors.affiliation: Department of Anatomy, Physiology & Cell Biology, School of Veterinary Medicine, University of California, 4206 VM3A, 1285 Veterinary Medicine Drive, Davis, CA 95616, USA.
authors.forename: Leah Forquer
authors.initials: LF
authors.lastname: Raheja
authors.forename: Damian C
authors.initials: DC
authors.lastname: Genetos
authors.forename: Clare E
authors.initials: CE
authors.lastname: Yellowley
mesh_terms: D015687:Cell Hypoxia / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D009500:Neutralization Tests; D010011:Osteocytes / Q000166:cytology* / Q000187:drug effects; D053495:Osteopontin / Q000378:metabolism* / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D017077:Culture Media, Conditioned; D018960:Hyaluronan Receptors; D011994:Recombinant Proteins; D053495:Osteopontin