-
Development (Cambridge, England) Apr 2022The mechanisms underlying bone development, repair and regeneration are reliant on the interplay and communication between osteoclasts and other surrounding cells.... (Review)
Review
The mechanisms underlying bone development, repair and regeneration are reliant on the interplay and communication between osteoclasts and other surrounding cells. Osteoclasts are multinucleated monocyte lineage cells with resorptive abilities, forming the bone marrow cavity during development. This marrow cavity, essential to hematopoiesis and osteoclast-osteoblast interactions, provides a setting to investigate the origin of osteoclasts and their multi-faceted roles. This Review examines recent developments in the embryonic understanding of osteoclast origin, as well as interactions within the immune environment to regulate normal and pathological bone development, homeostasis and repair.
Topics: Bone Development; Bone Resorption; Cell Differentiation; Homeostasis; Humans; Osteoclasts
PubMed: 35502779
DOI: 10.1242/dev.199908 -
Endocrine Reviews Jun 2016Notch 1 to 4 receptors are important determinants of cell fate and function, and Notch signaling plays an important role in skeletal development and bone remodeling.... (Review)
Review
Notch 1 to 4 receptors are important determinants of cell fate and function, and Notch signaling plays an important role in skeletal development and bone remodeling. After direct interactions with ligands of the Jagged and Delta-like families, a series of cleavages release the Notch intracellular domain (NICD), which translocates to the nucleus where it induces transcription of Notch target genes. Classic gene targets of Notch are hairy and enhancer of split (Hes) and Hes-related with YRPW motif (Hey). In cells of the osteoblastic lineage, Notch activation inhibits cell differentiation and causes cancellous bone osteopenia because of impaired bone formation. In osteocytes, Notch1 has distinct effects that result in an inhibition of bone resorption secondary to an induction of osteoprotegerin and suppression of sclerostin with a consequent enhancement of Wnt signaling. Notch1 inhibits, whereas Notch2 enhances, osteoclastogenesis and bone resorption. Congenital disorders of loss- and gain-of-Notch function present with severe clinical manifestations, often affecting the skeleton. Enhanced Notch signaling is associated with osteosarcoma, and Notch can influence the invasive potential of carcinoma of the breast and prostate. Notch signaling can be controlled by the use of inhibitors of Notch activation, small peptides that interfere with the formation of a transcriptional complex, or antibodies to the extracellular domain of specific Notch receptors or to Notch ligands. In conclusion, Notch plays a critical role in skeletal development and homeostasis, and serious skeletal disorders can be attributed to alterations in Notch signaling.
Topics: Animals; Bone Development; Bone Diseases, Developmental; Humans; Receptors, Notch; Signal Transduction
PubMed: 27074349
DOI: 10.1210/er.2016-1002 -
International Journal of Molecular... Apr 2015MicroRNAs (miRNAs) are endogenous small noncoding ~22-nt RNAs, which have been reported to play a crucial role in maintaining bone development and metabolism.... (Review)
Review
MicroRNAs (miRNAs) are endogenous small noncoding ~22-nt RNAs, which have been reported to play a crucial role in maintaining bone development and metabolism. Osteogenesis originates from mesenchymal stem cells (MSCs) differentiating into mature osteoblasts and each period of bone formation is inseparable from the delicate regulation of various miRNAs. Of note, apprehending the sophisticated circuit between miRNAs and osteogenic homeostasis is of great value for artificial skeletal regeneration for severe bone defects. In this review, we highlight how different miRNAs interact with diverse osteo-related genes and endeavor to sketch the contours of potential manipulations of miRNA-modulated bone repair.
Topics: Animals; Bone Development; Bone and Bones; Cell Differentiation; Humans; MicroRNAs; Osteoblasts; Osteogenesis; Regeneration
PubMed: 25872144
DOI: 10.3390/ijms16048227 -
International Journal of Molecular... Apr 2021Bone development is a tightly regulated process. Several integrated signaling pathways including HH, PTHrP, WNT, NOTCH, TGF-β, BMP, FGF and the transcription factors... (Review)
Review
Bone development is a tightly regulated process. Several integrated signaling pathways including HH, PTHrP, WNT, NOTCH, TGF-β, BMP, FGF and the transcription factors SOX9, RUNX2 and OSX are essential for proper skeletal development. Misregulation of these signaling pathways can cause a large spectrum of congenital conditions categorized as skeletal dysplasia. Since the signaling pathways involved in skeletal dysplasia interact at multiple levels and have a different role depending on the time of action (early or late in chondrogenesis and osteoblastogenesis), it is still difficult to precisely explain the physiopathological mechanisms of skeletal disorders. However, in recent years, significant progress has been made in elucidating the mechanisms of these signaling pathways and genotype-phenotype correlations have helped to elucidate their role in skeletogenesis. Here, we review the principal signaling pathways involved in bone development and their associated skeletal dysplasia.
Topics: Animals; Bone Development; Humans; Osteochondrodysplasias; Signal Transduction
PubMed: 33919228
DOI: 10.3390/ijms22094321 -
The Journal of Clinical Endocrinology... Mar 2021Exposed surfaces of mammals are colonized with 100 trillion indigenous bacteria, fungi, and viruses, creating a diverse ecosystem known as the human microbiome. The gut... (Review)
Review
Exposed surfaces of mammals are colonized with 100 trillion indigenous bacteria, fungi, and viruses, creating a diverse ecosystem known as the human microbiome. The gut microbiome is the richest microbiome and is now known to regulate postnatal skeletal development and the activity of the major endocrine regulators of bone. Parathyroid hormone (PTH) is one of the bone-regulating hormone that requires elements of the gut microbiome to exert both its bone catabolic and its bone anabolic effects. How the gut microbiome regulates the skeletal response to PTH is object of intense research. Involved mechanisms include absorption and diffusion of bacterial metabolites, such as short-chain fatty acids, and trafficking of immune cells from the gut to the bone marrow. This review will focus on how the gut microbiome communicates and regulates bone marrow cells in order to modulate the skeletal effects of PTH.
Topics: Animals; Bone Development; Bone Marrow; Bone Marrow Cells; Bone Remodeling; Bone and Bones; Gastrointestinal Microbiome; Humans; Parathyroid Hormone
PubMed: 33254225
DOI: 10.1210/clinem/dgaa895 -
Current Osteoporosis Reports Jun 2020Skeletal stem cells (SSCs) are considered to play important roles in bone development and repair. These cells have been historically defined by their in vitro potential... (Review)
Review
PURPOSE OF REVIEW
Skeletal stem cells (SSCs) are considered to play important roles in bone development and repair. These cells have been historically defined by their in vitro potential for self-renewal and differentiation into "trilineage" cells; however, little is known about their in vivo identity. Here, we discuss recent progress on SSCs and how they potentially contribute to bone development and repair.
RECENT FINDINGS
Bone is composed of diverse tissues, which include cartilage and its perichondrium, cortical bone and its periosteum, and bone marrow and its trabecular bone and stromal compartment. We are now at the initial stage of understanding the precise identity of SSCs in each bone tissue. The emerging concept is that functionally dedicated SSCs are encased by their own unique cellular and extracellular matrix microenvironment, and locally support its own compartment. Diverse groups of SSCs are likely to work in concert to achieve development and repair of the highly functional skeletal organ.
Topics: Adipocytes; Adult Stem Cells; Bone Development; Bone Marrow; Bone Marrow Cells; Bone Regeneration; Cancellous Bone; Cartilage; Cell Differentiation; Cell Lineage; Chondrocytes; Cortical Bone; Growth Plate; Humans; Mesenchymal Stem Cells; Osteoblasts
PubMed: 32172443
DOI: 10.1007/s11914-020-00572-9 -
Journal of Bone and Mineral Research :... Aug 2021Osteoblasts are the only cells that can give rise to bones in vertebrates. Thus, one of the most important functions of these metabolically active cells is mineralized... (Review)
Review
Osteoblasts are the only cells that can give rise to bones in vertebrates. Thus, one of the most important functions of these metabolically active cells is mineralized matrix production. Because osteoblasts have a limited lifespan, they must be constantly replenished by preosteoblasts, their immediate precursors. Because disruption of the regulation of bone-forming osteoblasts results in a variety of bone diseases, a better understanding of the origin of these cells by defining the mechanisms of bone development, remodeling, and regeneration is central to the development of novel therapeutic approaches. In recent years, substantial new insights into the origin of osteoblasts-largely owing to rapid technological advances in murine lineage-tracing approaches and other single-cell technologies-have been obtained. Collectively, these findings indicate that osteoblasts involved in bone formation under various physiological, pathological, and therapeutic conditions can be obtained from numerous sources. The origins of osteoblasts include, but are not limited to, chondrocytes in the growth plate, stromal cells in the bone marrow, quiescent bone-lining cells on the bone surface, and specialized fibroblasts in the craniofacial structures, such as sutures and periodontal ligaments. Because osteoblasts can be generated from local cellular sources, bones can flexibly respond to regenerative and anabolic cues. However, whether osteoblasts derived from different cellular sources have distinct functions remains to be investigated. Currently, we are at the initial stage to aptly unravel the incredible diversity of the origins of bone-forming osteoblasts. © 2021 American Society for Bone and Mineral Research (ASBMR).
Topics: Animals; Bone Development; Bone and Bones; Growth Plate; Mice; Osteoblasts; Osteogenesis
PubMed: 34213032
DOI: 10.1002/jbmr.4410 -
Frontiers in Immunology 2019
Topics: Animals; Biomarkers; Bone Development; Bone and Bones; Disease Susceptibility; Humans; Osteocytes; Signal Transduction
PubMed: 31798574
DOI: 10.3389/fimmu.2019.02595 -
Journal of Strength and Conditioning... May 2022Pashkova, A, Hartman, JM, Letuchy, EM, and Janz, KF. Interscholastic athletics and bone strength: the Iowa bone development study. J Strength Cond Res 36(5): 1271-1276,...
Pashkova, A, Hartman, JM, Letuchy, EM, and Janz, KF. Interscholastic athletics and bone strength: the Iowa bone development study. J Strength Cond Res 36(5): 1271-1276, 2022-The objective of this study was to determine the relationship between adolescents' participation in various interscholastic sports and differences in bone strength outcomes. Subjects (N = 380) were recruited from the Iowa Bone Development Study and categorized based on sport participation into 3 power groups: no-power, low-power, and high-power. Sports such as basketball, cheerleading/poms, gymnastics, volleyball, track, football, tennis, and soccer were considered high-power. Peripheral quantitative computed tomography (pQCT) was used to determine bone measures of polar stress-strain index (measure of torsion strength), cortical content (measure of cortical bone size and area at the 66% tibia site), and bone strength index (measure of compression strength based on total bone density and area at the 4% tibia site). Adjusted pairwise comparison for group least squares means high-power sport participation compared with no-power sport participation showed significant differences in all bone strength outcomes for both men and women (p value < 0.01). There was a significant difference in all bone strength measures between low-power and no-power groups for men (p value < 0.05), but not women. Because of decreasing levels of physical activity in late adolescence, the promotion of high-power sports may be particularly important for optimal bone development in the final years before peak bone mass.
Topics: Adolescent; Bone Density; Bone Development; Bone and Bones; Female; Gymnastics; Humans; Male; Tibia
PubMed: 32459739
DOI: 10.1519/JSC.0000000000003646 -
Open Biology Oct 2019Skeletal vasculature plays a central role in the maintenance of microenvironments for osteogenesis and haematopoiesis. In addition to supplying oxygen and nutrients,... (Review)
Review
Skeletal vasculature plays a central role in the maintenance of microenvironments for osteogenesis and haematopoiesis. In addition to supplying oxygen and nutrients, vasculature provides a number of inductive factors termed as angiocrine signals. Blood vessels drive recruitment of osteoblast precursors and bone formation during development. Angiogenesis is indispensable for bone repair and regeneration. Dysregulation of the angiocrine crosstalk is a hallmark of ageing and pathobiological conditions in the skeletal system. The skeletal vascular bed is complex, heterogeneous and characterized by distinct capillary subtypes (type H and type L), which exhibit differential expression of angiocrine factors. Furthermore, distinct blood vessel subtypes with differential angiocrine profiles differentially regulate osteogenesis and haematopoiesis, and drive disease states in the skeletal system. This review provides an overview of the role of angiocrine signals in bone during homeostasis and disease.
Topics: Animals; Autocrine Communication; Bone Development; Bone Diseases; Homeostasis; Humans; Neovascularization, Physiologic
PubMed: 31575330
DOI: 10.1098/rsob.190144