Bone Marrow Cavity Formation Research Articles

Osteoclast differentiation and dynamic mRNA expression during mice embryonic palatal bone development

This study is the first to investigate the process of osteoclast (OCL) differentiation, its potential functions, and the associated mRNA and signalling pathways in embryonic palatal bone. Our findings suggest that OCLs are involved in bone remodelling, bone marrow cavity formation, and blood vessel formation in embryonic palatal bone. We observed TRAP-positive OCLs at embryonic day 16.5 (E16.5), E17.5, and E18.5 at the palatal process of the palate (PPP) and posterior and anterior parts of the palatal process of the maxilla (PPMXP and PPMXA, respectively), with OCL differentiation starting 2 days prior to TRAP positivity. By comparing the key periods of OCL differentiation between PPMX and PPP (E14.5, E15.5, and E16.5) using RNA-seq data of the palates, we found that the PI3K-AKT and MAPK signalling pathways were sequentially enriched, which may play critical roles in OCL survival and differentiation. Csf1r, Tnfrsff11a, Ctsk, Fos, Tyrobp, Fcgr3, and Spi1 were significantly upregulated, while Pik3r3, Tgfbr1, and Mapk3k7 were significantly downregulated, in both PPMX and PPP. Interestingly, Tnfrsff11b was upregulated in PPMX but downregulated in PPP, which may regulate the timing of OCL appearance. These results contribute to the limited knowledge regarding mRNA-specific steps in OCL differentiation in the embryonic palatal bone.

Osteoclasts and Macrophages—Their Role in Bone Marrow Cavity Formation During Mouse Embryonic Development

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 fourfold 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, whereas 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. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Role of macrophages in bone marrow cavity formation

Role of macrophages in bone marrow cavity formation

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

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

A rare cause of neonatal hypocalcemia: malignant infantile osteopetrosis

Malignant infantile osteopetrosis (MIOP) is a rare inherited bone disease characterized by reduced or dysregulated activity of osteoclasts, which results in generalized osteosclerosis. This leads to abnormal bone marrow cavity formation and to the clinical signs and symptoms of bone marrow failure and nerve compression. Symptoms related to early or late hypocalcemia may appear as the first presentation of MIOP in a newborn. We present a 14-day-old boy with neonatal hypocalcaemia due to MIOP.

Effect of macrophage colony-stimulating factor on osteoclast differentiation and the relevant morphologic modification in the mandibular condyle of osteopetrotic (op/op) mice

Osteopetrotic (op/op) mice have a prominent deficiency of osteoclasts caused by the absence of functional macrophage colony-stimulating factor (M-CSF). In the present study, we examined bone formation of the mandibular condyle after consecutive injections of M-CSF using 5 days-old mutant mice. In the M-CSF injected op/op mice, bone resorption on the inner surface of the mandibular ramus was noted at 10 days after birth, normally five days after the start of M-CSF injections, while there was no signs for bone resorption in untreated op/op mice of the some age. This activity increased with the progress in bone marrow cavity formation on postnatal day 15 and there after. In untreated op/op mice the condylar heads were still composed of cartilage tissue at even 25 days after birth. The op/op mice treated by M-CSF may provide us with new knowledge not only about the role of M-CSF in osteoclast differentiation in the mandible but also about the correlations in bone remodeling and morphology of the mandibular condyle and ramus.

Autosomal recessive osteopetrosis: diagnosis, management, and outcome

Autosomal recessive “malignant” osteopetrosis is a rare congenital disorder of bone resorption. It is caused by the failure of osteoclasts to resorb immature bone.1-3 This leads to abnormal bone marrow...

Morphological study of recombinant human transforming growth factor β1-induced intramembranous ossification in neonatal rat parietal bone

Recombinant human transforming growth factor β 1 (rhu TGF β 1) was injected singly or repeatedly for 3–12 days into the periosteum of the right side parietal bone of neonatal rats under the period of bone growth, and the time course of histological changes of the bone was observed by light and electron microscopy and by enzyme histochemistry. The repeated injections of rhu TGF β 1 at 200 ng/day increased the thickness of the bone tissue on the treated side, which was about twice the nontreated side value after 12-day injections. On the dermal side, preosteoblasts in the periosteum increased in an early stage of treatment, and thereafter, differentiation into osteoblasts, increase of bone matrix, bone marrow cavity formation, and increase of osteoclasts within the bone marrow cavities were observed. Activation of osteoblasts on the dura mater side was also seen. The single injection of rhu TGF β 1 at 200 ng resulted only in increased osteoprogenitor cell layers and bone matrix formation in an early stage, and the thickness of the osteoprogenitor cell layers and bone tissue at 12 days after single injection was comparable to the values on the nontreated side. At 1 μg, however, the osteoblasts were activated, and the osteoprogenitor cell layers and bone matrix formation were markedly increased. At 12 days, the bone tissue thickness on the treated side was about twice the nontreated side value, as in the repeated treatment groups. As described above, the 12-day repeated or single treatment of rhu TGF β 1, to the neonatal rat parietal bone (membrane bone) induced marked proliferation of preosteoblasts and promoted bone formation. No cartilage formation was seen in any group.

Ultrastructure of the tibial epiphyseal growth plate in microphthalmic (mi/mi) mice

Osteoclasts from growth plates of affected (mi/mi) and control (mi/+) microphthalmic mice, from newborn to 15 days old, were examined. Osteoclasts from unaffected mice were generally large, multinucleated cells with distinct ruffled borders and clear zones. Osteoclasts from the mi/mi litter mates were predominantly mononucleated, lacking in ruffled borders, clear zones and an abundance of organelles, features not normally associated with a functioning resorptive cell. The lamina limitans was more distinct in mi/mi mice. By 15 days, no evidence of bone resorption was seen in mi/mi mice. The immature appearance of osteoclasts and the lack of bone marrow cavity formation in mi/mi mice may result from either a fusion defect or from a limited life span of osteoclasts.