Bone dynamics is involved in the regulation of healthy and clonal hematopoiesis, while hematopoietic cells participate in bone remodeling and healing. By producing cytokines and extracellular matrix, osteolineage cells influence bone marrow-residing hematopoietic stem and progenitor cells (HSPCs) and differentiation into mature blood cells. Osteolineage cells promote the retention of quiescent HSPCs residing in the endosteal niche between bone and bone marrow, thus organizing the osteohematopoietic niche. Leukemic cells and disseminated tumor cells compete with healthy HSPCs for (osteohematopoietic) niche occupation, leading to the structural and functional changes in osteolineage compartments affecting bone health. A number of current studies aim to identify the osteolineage cell profile in hematopoiesis in aging, infection, (non)-myeloablative conditioning, or neoplasia. Skeletal maintenance and hematopoiesis are energy-demanding processes, meaning there would be great benefits identifying the metabolic pathways that coordinate these processes. Ultimately, this would reveal potential therapeutic targets in pharmaco-resistant settings and outcome predictions.
Along with mechanical and metabolic functions, the skeletal system acts as an endocrine-like organ, controlling whole-organism energy metabolism. Showing the capacity to store metabolites, hormones, and fat, the skeletal system coordinates the process of hematopoiesis. Metabolic pathways triggered by PTH receptor activation, IL-6, RANKL, Jagged1 expression and Notch signaling in osteoblasts, connect the close communication between osteoblastic cells and HSPCs. Maintaining the balance of intrinsic and extrinsic factors in the osteohematopoietic niche requires fine regulation. The activation of bone resorption phases involves pathways associated with HSPC mobilization and myeloid differentiation, where HSPC-derived osteoclasts promote HSPC mobilization. Improvement of skeletal health by established drugs can be associated with hematopoietic autophagy and deleterious effects. However, HSPCs alter osteoclast maturation, while underlying cell-autonomous and nonautonomous pathways are not fully revealed. In blood cancers, predominantly multiple myeloma but also myelodysplastic syndromes, leukemia, the neoplastic blood cells cause uncoupling of the bone remodelling and stimulate cancer progression. Although metabolic pathways and endocrine factors, such as erythropoietin, PTH, and estrogens are known to participate in the osteohematopoietic niche(s), their role in communication between osteolineage and hematopoietic cells is poorly understood. More direct evidence is needed to demonstrate correlations among bone phenotype, niche alterations, and hematopoietic functions.
Authors are invited to contribute to the Research Topic by submitting their work related to osteohematopoietic niche crosstalk in inflammation, aging, and neoplasms. Crosstalk of skeletal and hematopoietic systems is to be explored in the context of pathways involved in:
• Metabolic regulation of bone formation, remodeling, and healing.
• Metabolic, inflammatory, and malignant bone diseases.
• Premalignant and pre-metastatic skeletal niche formation.
• Aged bone marrow niche.
• Roles of endocrine hormones, mitochondria, and calcium signaling.
• Metabolic regulation of hematopoietic cell maintenance, mobilization, and differentiation.
• Clonal hematopoiesis and malignancies (myelodysplastic syndromes, leukemia, and multiple myeloma).
Keywords:
Bone, hematopoiesis, malignancy, osteohematopoietic niche, osteoblasts, osteoclasts, metabolism, hormones.
Important Note:
All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
Bone dynamics is involved in the regulation of healthy and clonal hematopoiesis, while hematopoietic cells participate in bone remodeling and healing. By producing cytokines and extracellular matrix, osteolineage cells influence bone marrow-residing hematopoietic stem and progenitor cells (HSPCs) and differentiation into mature blood cells. Osteolineage cells promote the retention of quiescent HSPCs residing in the endosteal niche between bone and bone marrow, thus organizing the osteohematopoietic niche. Leukemic cells and disseminated tumor cells compete with healthy HSPCs for (osteohematopoietic) niche occupation, leading to the structural and functional changes in osteolineage compartments affecting bone health. A number of current studies aim to identify the osteolineage cell profile in hematopoiesis in aging, infection, (non)-myeloablative conditioning, or neoplasia. Skeletal maintenance and hematopoiesis are energy-demanding processes, meaning there would be great benefits identifying the metabolic pathways that coordinate these processes. Ultimately, this would reveal potential therapeutic targets in pharmaco-resistant settings and outcome predictions.
Along with mechanical and metabolic functions, the skeletal system acts as an endocrine-like organ, controlling whole-organism energy metabolism. Showing the capacity to store metabolites, hormones, and fat, the skeletal system coordinates the process of hematopoiesis. Metabolic pathways triggered by PTH receptor activation, IL-6, RANKL, Jagged1 expression and Notch signaling in osteoblasts, connect the close communication between osteoblastic cells and HSPCs. Maintaining the balance of intrinsic and extrinsic factors in the osteohematopoietic niche requires fine regulation. The activation of bone resorption phases involves pathways associated with HSPC mobilization and myeloid differentiation, where HSPC-derived osteoclasts promote HSPC mobilization. Improvement of skeletal health by established drugs can be associated with hematopoietic autophagy and deleterious effects. However, HSPCs alter osteoclast maturation, while underlying cell-autonomous and nonautonomous pathways are not fully revealed. In blood cancers, predominantly multiple myeloma but also myelodysplastic syndromes, leukemia, the neoplastic blood cells cause uncoupling of the bone remodelling and stimulate cancer progression. Although metabolic pathways and endocrine factors, such as erythropoietin, PTH, and estrogens are known to participate in the osteohematopoietic niche(s), their role in communication between osteolineage and hematopoietic cells is poorly understood. More direct evidence is needed to demonstrate correlations among bone phenotype, niche alterations, and hematopoietic functions.
Authors are invited to contribute to the Research Topic by submitting their work related to osteohematopoietic niche crosstalk in inflammation, aging, and neoplasms. Crosstalk of skeletal and hematopoietic systems is to be explored in the context of pathways involved in:
• Metabolic regulation of bone formation, remodeling, and healing.
• Metabolic, inflammatory, and malignant bone diseases.
• Premalignant and pre-metastatic skeletal niche formation.
• Aged bone marrow niche.
• Roles of endocrine hormones, mitochondria, and calcium signaling.
• Metabolic regulation of hematopoietic cell maintenance, mobilization, and differentiation.
• Clonal hematopoiesis and malignancies (myelodysplastic syndromes, leukemia, and multiple myeloma).
Keywords:
Bone, hematopoiesis, malignancy, osteohematopoietic niche, osteoblasts, osteoclasts, metabolism, hormones.
Important Note:
All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.