Osteal macrophages support physiologic skeletal remodeling and anabolic actions of parathyroid hormone in bone

Sun Wook Cho, Fabiana N. Soki, Amy J. Koh, Matthew R. Eber, Payam Entezami, Serkin Park, Nico Van Rooijen, Laurie K. McCauley

Research output: Contribution to journalArticle

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Abstract

Cellular subpopulations in the bone marrow play distinct and unexplored functions in skeletal homeostasis. This study delineated a unique role of osteal macrophages in bone and parathyroid hormone (PTH)-dependent bone anabolism using murine models of targeted myeloid-lineage cell ablation. Depletion of c-fms+ myeloid lineage cells [via administration of AP20187 in the macrophage Fas-induced apoptosis (MAFIA) mouse model] reduced cortical and trabecular bone mass and attenuated PTHinduced trabecular bone anabolism, supporting the positive function of macrophages in bone homeostasis. Interestingly, using a clodronate liposome model with targeted depletion of mature phagocytic macrophages an opposite effect was found with increased trabecular bone mass and increased PTH-induced anabolism. Apoptotic cells were more numerous in MAFIA versus clodronate-treated mice and flow cytometric analyses of myeloid lineage cells in the bone marrow showed that MAFIA mice had reduced CD68+ cells, whereas clodronate liposome-treated mice had increased CD68+ and CD163+ cells. Clodronate liposomes increased efferocytosis (clearance of apoptotic cells) and gene expression associated with alternatively activated M2 macrophages as well as expression of genes associated with bone formation including Wnt3a, Wnt10b, and Tgfb1. Taken together, depletion of early lineage macrophages resulted in osteopenia with blunted effects of PTH anabolic actions, whereas depletion of differentiated macrophages promoted apoptotic cell clearance and transformed the bone marrow to an osteogenic environment with enhanced PTH anabolism. These data highlight a unique function for osteal macrophages in skeletal homeostasis.

Original languageEnglish
Pages (from-to)1545-1550
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number4
DOIs
Publication statusPublished - 2014 Jan 28
Externally publishedYes

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Parathyroid Hormone
Macrophages
Bone and Bones
Clodronic Acid
Myeloid Cells
Liposomes
Homeostasis
Bone Marrow
Apoptosis
Gene Expression
Metabolic Bone Diseases
Osteogenesis

ASJC Scopus subject areas

  • General

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Osteal macrophages support physiologic skeletal remodeling and anabolic actions of parathyroid hormone in bone. / Cho, Sun Wook; Soki, Fabiana N.; Koh, Amy J.; Eber, Matthew R.; Entezami, Payam; Park, Serkin; Van Rooijen, Nico; McCauley, Laurie K.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 4, 28.01.2014, p. 1545-1550.

Research output: Contribution to journalArticle

Cho, Sun Wook ; Soki, Fabiana N. ; Koh, Amy J. ; Eber, Matthew R. ; Entezami, Payam ; Park, Serkin ; Van Rooijen, Nico ; McCauley, Laurie K. / Osteal macrophages support physiologic skeletal remodeling and anabolic actions of parathyroid hormone in bone. In: Proceedings of the National Academy of Sciences of the United States of America. 2014 ; Vol. 111, No. 4. pp. 1545-1550.
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