Osteoclasts and macrophages - their role in bone marrow cavity formation during mouse embryonic development
Journal Title
Journal of Bone and Mineral Research
Publication Type
epub ahead of print
The formation of the bone marrow cavity is a prerequisite for endochondral ossification. In reviews and textbooks, it is occasionally reported that osteoclasts are essential for bone marrow cavity formation removing hypertrophic chondrocytes. Mice lacking osteoclasts or having functionally defective osteoclasts have osteopetrotic bones, yet, they still form a bone marrow cavity. Here, we investigated the role of osteoclasts and macrophages in bone marrow cavity formation during embryogenesis. Macrophages can assist osteoclasts in matrix-removal by phagocytosing resorption byproducts. Rank-deficient mice, lacking osteoclasts, and Pu.1-deficient mice, lacking monocytes, macrophages, and osteoclasts, displayed a delay in bone marrow cavity formation and a lengthening of the zone of hypertrophic chondrocytes. F4/80 positive monocyte/macrophage numbers increased by about four-fold in the bone marrow cavity of E18.5 Rank-deficient mice. Based on lineage-tracing experiments, the majority of the excess F4/80 cells were derived from definitive hematopoietic precursors of the fetal liver. In long bones of both Rank(-/-) and Pu.1(-/-) specimens, Mmp9-positive cells were still present. In addition to monocytes, macrophages, and osteoclasts, Ctsb-positive septoclasts were lost in Pu.1(-/-) specimens. The mineralization pattern was altered in Rank(-/-) and Pu.1(-/-) specimens, revealing a significant rise in transverse-oriented mineralized structures. Taken together our findings imply that early on during bone marrow cavity formation osteoclasts facilitate the entry of blood vessels and later the turnover of hypertrophic chondrocytes, while macrophages appear to play no major role. Furthermore, the absence of septoclasts in Pu.1(-/-) specimens suggests that septoclasts are either derived from Pu.1-dependent precursors or require PU.1 activity for their differentiation. This article is protected by copyright. All rights reserved.
bone marrow cavity formation; hypertrophic chondrocyte turnover; macrophage; osteoclast; septoclast
WEHI Research Division(s)
PubMed ID
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Creation Date: 2022-06-17 09:28:58
Last Modified: 2022-06-17 10:00:01
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