title: Acceleration of bone repair in NOD/SCID mice by human monoosteophils, novel LL-37-activated monocytes.
abstract: BACKGROUND
  An incomplete understanding of bone forming cells during wound healing and ectopic calcification has led to a search for circulating cells that may fulfill this function. Previously, we showed that monoosteophils, a novel lineage of calcifying/bone-forming cells generated by treatment of monocytes with the natural peptide LL-37, are candidates. In this study, we have analyzed their gene expression profile and bone repair function.
  
  
  RESULTS
  Human monoosteophils can be distinguished from monocytes, macrophages and osteoclasts by their unique up-regulation of integrin α3 and down-regulation of CD14 and CD16. Monoosteophils express high mRNA and protein levels of SPP1 (osteopontin), GPNMB (osteoactivin), CHI3L1 (cartilage glycoprotein-39), CHIT1 (Chitinase 1), MMP-7, CCL22 and MAPK13 (p38MAPKδ). Monocytes from wild type, but not MAPK13 KO mice are also capable of monoosteophil differentiation, suggesting that MAPK13 regulates this process. When human monoosteophils were implanted in a freshly drilled hole in mid-diaphyseal femurs of NOD/SCID mice, significant bone repair required only 14 days compared to at least 24 days in control treated injuries.
  
  
  CONCLUSIONS
  Human derived monoosteophils, characterized as CD45(+)α3(+)α3β(+)CD34(-)CD14(-)BAP (bone alkaline phosphatase)(-) cells, can function in an animal model of bone injury.
authors.affiliation: Department of Immunology, Beckman Research Institute of City of Hope, Duarte, California, United States of America.
authors.forename: Zhifang
authors.initials: Z
authors.lastname: Zhang
authors.forename: John E
authors.initials: JE
authors.lastname: Shively
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects / Q000235:genetics; D002113:Calcification, Physiologic; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation; D054422:Chemokine CCL22 / Q000096:biosynthesis; D002688:Chitinases / Q000096:biosynthesis; D005136:Eye Proteins / Q000096:biosynthesis; D020869:Gene Expression Profiling; D006801:Humans; D016130:Immunophenotyping; D008264:Macrophages / Q000378:metabolism; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D048292:Mitogen-Activated Protein Kinase 13 / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism; D010011:Osteocytes / Q000187:drug effects* / Q000378:metabolism*; D053495:Osteopontin / Q000096:biosynthesis; D015398:Signal Transduction; D054804:Cathelicidins
chemical_list: D000954:Antigens, Surface; D023181:Antimicrobial Cationic Peptides; D054422:Chemokine CCL22; D005136:Eye Proteins; C445671:Gpnmb protein, mouse; D008562:Membrane Glycoproteins; D053495:Osteopontin; D048292:Mitogen-Activated Protein Kinase 13; D002688:Chitinases; D020783:Matrix Metalloproteinase 7; D054804:Cathelicidins