title: Cutting edge: Parathyroid hormone facilitates macrophage efferocytosis in bone marrow via proresolving mediators resolvin D1 and resolvin D2.
abstract: Bone marrow macrophages stimulate skeletal wound repair and osteoblastic bone formation by poorly defined mechanisms. Specialized proresolving mediators of inflammation drive macrophage efferocytosis (phagocytosis of apoptotic cells) and resolution, but little is known regarding this process in the bone marrow. In this study, metabololipidomic profiling via liquid chromatography mass spectrometry revealed higher levels of specialized proresolving mediators in the bone marrow relative to the spleen. The endocrine and bone anabolic agent parathyroid hormone increased specialized proresolving mediator levels, including resolvins (Rvs), in bone marrow. Human and murine primary macrophages efferocytosed apoptotic osteoblasts in vitro, and RvD1 and RvD2 (10 pM-10 nM) enhanced this process. These findings support a unique profile of specialized lipid mediators in bone marrow that contribute to a feedback system for resolution of inflammation and maintenance of skeletal homeostasis.
authors.affiliation: School of Dentistry, University of Michigan, Ann Arbor, MI 48109; Department of Pathology, Medical School, University of Michigan, Ann Arbor, MI 48109; and mccauley@umich.edu.
authors.forename: Laurie K
authors.initials: LK
authors.lastname: McCauley
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Institutes of Medicine, Boston, MA 02115.
authors.forename: Jesmond
authors.initials: J
authors.lastname: Dalli
authors.affiliation: School of Dentistry, University of Michigan, Ann Arbor, MI 48109;
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Koh
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Institutes of Medicine, Boston, MA 02115.
authors.forename: Nan
authors.initials: N
authors.lastname: Chiang
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Institutes of Medicine, Boston, MA 02115.
authors.forename: Charles N
authors.initials: CN
authors.lastname: Serhan
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology*; D002478:Cells, Cultured; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D008297:Male; D051379:Mice; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010587:Phagocytosis / Q000187:drug effects*
chemical_list: D010281:Parathyroid Hormone; C518399:resolvin D1; C545423:resolvin D2; D004281:Docosahexaenoic Acids