Role of CSF-1 in bone and bone marrow development

Abstract

There is a close interaction between the processes involved in osteogenesis and hemopoiesis. In developing bone, the osteoclasts, cells of hemopoietic origin, resorb and invade the calcified cartilage rudiment. As a result, the primitive marrow cavity is formed and hemopoiesis initiates. Osteogenic cells—osteoblasts and osteocytes—control the development and activity of the osteoclasts through the local release of factors. One factor responsible for this osteoblast‐osteoclast interaction is colony‐stimulating factor‐1 (CSF‐1). Studies performed on the osteopetrotic op/op mouse mutant have established that this factor is essential for proliferation and differentiation of the osteoclasts. Expression of CSF‐1 receptors by mature osteoclasts and osteoclast precursors strongly suggests that CSF‐1 action is exerted directly on cells of this lineage. In vivo, CSF‐1 synthesis by osteoblasts is temporally and spatially related to sites of osteoclast development. Thus CSF‐1 may represent one of the factors responsible for coupling hemopoiesis to osteogenesis. In vitro, osteoblasts express at least 4 transcripts encoding either a secreted or a membrane‐bound form of CSF‐1. At the protein level, osteoblasts in vitro synthesize the membrane‐bound form and secrete the majority of CSF‐1 as a proteoglycan, a small fraction of which is integrated into the matrix. These different molecular forms may locally restrict the biological action of this cytokine. Indeed, injection of recombinant human CSF‐1 in op/op mutants does not correct the osteoclast deficiency in the metaphyseal spongiosa of long bones, and sclerosis persists at this site. Similarly, the deficiency of some tissue macrophage populations in op/op mice is only partially or not at all corrected by injection of CSF‐1. The expression of CSF‐1 receptors by mature osteoclasts may imply that CSF‐1 also influences their bone resorbing activity. Indeed, CSF‐1 has been shown to induce osteoclast fusion, spreading, and survival. These findings suggest that CSF‐1 is essential for the proliferation, differentiation, activity, and survival of tissue macrophages and osteoclasts, cells involved in tissue turnover. Furthermore, they corroborate the view that both osteoclasts and tissue macrophages stem from a CSF‐1‐dependent common precursor along the macrophage lineage. Mol Reprod Dev 46:75–84, 1997. © 1997 Wiley‐Liss, Inc.

Expression of CSF1, AR, and SRD5A2 during Postnatal Development of the Boar Reproductive Tract

“…The relatively high expression of CSF1 in the juvenile testis and decreasing expression with age observed in this study are consistent with the contributory role of CSF1 in testicular development and maturation, as established in other organ systems [ 64 , 65 , 66 , 67 , 68 ]. Expression of testicular AR is highest at the prepubertal transition point, a time when circulating testosterone is low; increased expression of AR might be a compensatory mechanism.…”

Colony stimulating factor 1 receptor ( Csf1r ) expressing cell ablation in mafia (macrophage‐specific Fas‐induced apoptosis) mice alters monocyte landscape and atherosclerotic lesion characteristics

“…This rebound of the monocyte lineage has previously been described, but we are the first to link this replenishment to increased extramedullary hematopoiesis and to provide proof that this is accompanied by a shift in circulating monocyte subset distribution toward a nonclassical phenotype [11]. The production and release of myeloid progenitors in the bone marrow are controlled by osteoclasts [39], which express several macrophage surface markers, including CSF1R [4], and which were depleted as well after in vivo AP20187 treatment [4, 40]. The failing stromal myelopoiesis could have spurred extramedullary myelopoiesis in the spleen observed after prolonged depletion.…”

Single-Cell Landscape of the Cochlea Revealed Cell-Type-Specific Diversification in Hipposideros armiger Based on PacBio Long-Read Sequencing

“…Osteoblasts are bone-forming cells of mesenchymal origin and principal participants in bone cell biology, potentially specialized in maintaining skeletal integrity and sensing mechanical strain [ 87 ]. The pseudotime trajectory reveals the differentiation process of mesenchymal cells (MCs) into osteoblasts (OBs) (Branch 1) and fibrocytes (FCs) (Branch 2) ( Figure 6 A).…”

“…Among the genes regulated downstream of Runx2 ( Figure 6 D), many are associated with osteoblast development, such as colony stimulating factor 1 ( CSF1 ). CSF1 is an osteoblast-derived factor that directly promotes osteoclast development and serves as a crucial regulator of bone resorption [ 78 , 87 ]. It may also play a key role in the maturation of osteoblasts and chondrocytes.…”