Direct Resorption of Calcified Cartilage by Macrophages during Primary Bone Marrow Cavity Formation

抄録

Osteoclasts are the main cells to resorb calcified tissues. However, it is still uncertain whether cells other than osteoclasts can resorb calcified tissues. In this study, we investigated histologically the process of primary bone marrow cavity formation of humeral bone primordia. To inhibit resorption by osteoclasts, pregnant mice were treated with a daily administration of aminobisphosphonate, 4-amino-1-hydroxybutylidene-1,1-bisphosphonate (AHBuBP: 10 µmol/kg) from 15 to 17 days gestation stage (E15-E17) before the formation of fetal humeral bone marrow cavities. Although the number of primary bone trabecula increased with AHBuBP treatment, both humeral bones of newborn mice with/without AHBuBP treatment developed bone marrow cavities where active hematopoiesis was observed. In the AHBuBP treated group, osteoclasts attached to the surface of trabecula showed no clear zone nor ruffled border. At E16, a primary bone marrow cavity was formed. Ultrastructural study indicated that calcified cartilage became fragmented to form particles that were phagocytosed by macrophages. Furthermore, the density of collagen fibers in calcified cartilage decreased with the process of calcification. These results indicate a new resorption process of calcified tissue, that is the degradation of calcified cartilage and the phagocytosis of calcified cartilage particles by macrophages; in addition, this study suggests that osteoclasts might not be related to the onset of hematopoiesis in the bone marrow cavity.