Postnatal skeletal growth is driven by the epiphyseal stem cell niche: potential implications to pediatrics

Chagin, Andrei S.; Newton, Phillip T

doi:10.1038/s41390-019-0722-z

Cited by 31 publications

(28 citation statements)

References 48 publications

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“…At the neonatal age, bone growth is based on the consumption of chondroprogenitors. Postnatally, after the formation of the mineralized epiphyses, chondroprogenitors in an epiphyseal stem-cell niche acquire a unique PTHrP-positive skeletal stem cell phenotype, self-renew and proliferate and generate chondrocytes, which can transdifferentiate into osteoblasts and stromal cells (for review, [140]). Removal of woven or old bone by resorption is regulated by the receptor activator of NF-κB ligand (RANKL), which binds to its receptor RANK to stimulate osteoclast differentiation and activity [141].…”

Section: Bone Formation and Skeletogenesismentioning

confidence: 99%

The YAP/TAZ Pathway in Osteogenesis and Bone Sarcoma Pathogenesis

Kovar

Bierbaumer

Radic-Sarikas

2020

Cells

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YAP and TAZ are intracellular messengers communicating multiple interacting extracellular biophysical and biochemical cues to the transcription apparatus in the nucleus and back to the cell/tissue microenvironment interface through the regulation of cytoskeletal and extracellular matrix components. Their activity is negatively and positively controlled by multiple phosphorylation events. Phenotypically, they serve an important role in cellular plasticity and lineage determination during development. As they regulate self-renewal, proliferation, migration, invasion and differentiation of stem cells, perturbed expression of YAP/TAZ signaling components play important roles in tumorigenesis and metastasis. Despite their high structural similarity, YAP and TAZ are functionally not identical and may play distinct cell type and differentiation stage-specific roles mediated by a diversity of downstream effectors and upstream regulatory molecules. However, YAP and TAZ are frequently looked at as functionally redundant and are not sufficiently discriminated in the scientific literature. As the extracellular matrix composition and mechanosignaling are of particular relevance in bone formation during embryogenesis, post-natal bone elongation and bone regeneration, YAP/TAZ are believed to have critical functions in these processes. Depending on the differentiation stage of mesenchymal stem cells during endochondral bone development, YAP and TAZ serve distinct roles, which are also reflected in bone tumors arising from the mesenchymal lineage at different developmental stages. Efforts to clinically translate the wealth of available knowledge of the pathway for cancer diagnostic and therapeutic purposes focus mainly on YAP and TAZ expression and their role as transcriptional co-activators of TEAD transcription factors but rarely consider the expression and activity of pathway modulatory components and other transcriptional partners of YAP and TAZ. As there is a growing body of evidence for YAP and TAZ as potential therapeutic targets in several cancers, we here interrogate the applicability of this concept to bone tumors. To this end, this review aims to summarize our current knowledge of YAP and TAZ in cell plasticity, normal bone development and bone cancer.Cells 2020, 9, 972 2 of 34 co-activators Yes-associated protein 1 (YAP-1, YAP) and its paralogue, the transcriptional co-activator with PDZ-binding motif (TAZ, WWTR1), which are typically controlled on the post-translational level by upstream regulatory signaling pathways in organ development and tissue homeostasis [2,3]. YAP and TAZ were reported to affect self-renewal and lineage commitment of stem cells [4][5][6][7], while hyperactivation of YAP and TAZ have been linked to cancer growth and metastasis in various tumors [8][9][10]. TAZ levels are elevated in approximately 20% of cancers and drive invasion and metastasis [11,12], while YAP is frequently overexpressed or amplified in cancer and was shown to promote resistance to chemotherapy in oncogene-addicted tumors up...

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Section: Bone Formation and Skeletogenesismentioning

confidence: 99%

The YAP/TAZ Pathway in Osteogenesis and Bone Sarcoma Pathogenesis

Kovar

Bierbaumer

Radic-Sarikas

2020

Cells

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“…During childhood, longitudinal growth is determined by the activity of the growth plate cartilage located in the epiphyses of long bones [23]. Chondrocytes contained in the proliferative zone of the growth plates rapidly divide and organize themselves into columns that align parallel to the direction of growth.…”

Section: Bone Formation and Skeletal Growthmentioning

confidence: 99%

Rickets in Children: An Update

Gentile

Chiarelli

2021

Biomedicines

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Rickets refers to a deficient mineralization of the growth plate cartilage, predominantly affecting longer bones. Despite the fact that preventive measures are available, it is still a common disease worldwide; nutritional rickets, due to vitamin D deficiency or dietary calcium inadequate intake, remains the most common form. Medical history, physical examination, radiologic features and biochemical tests are essential for diagnosis. Although recent studies suggest hypophosphatemia as the leading alteration, rickets is classically divided into two categories: calcipenic rickets and phosphopenic rickets. Knowledge of this categorization and of respective clinical and laboratory features is essential for rapid diagnosis and correct management. The aim of this review is to analyze the epidemiological, pathogenetic, clinical, and therapeutic aspects of the different forms of rickets, describing the novelties on this “long-lived” disease.

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“…The stem cell niche in the growth plate, which we refer to as the epiphyseal stem cell niche ( Chagin and Newton, 2019 ), is probably formed by the SOC when it has matured so that bone cells and extracellular matrix is close to the ep-SSPCs ( Newton et al, 2019 ). The variety of cells present in the SOC include osteocytes, osteoblasts, stromal cells, mesenchymal cells, and hematopoietic cells of the bone marrow, as well as nerve fibers and the cells that form blood vessels.…”

Section: The Stem Cell Niche In the Epiphyseal Growth Platementioning

confidence: 99%

“…However, detailed determination of the components of this niche and their roles in the regulation of individual populations of SSPCs within the primary spongiosa will probably require approaches that are more advanced and sophisticated than those been utilized to date. Moreover, it is important to remember that in humans the growth plate fuses (disappears) during late puberty, in association with the cessation of growth, whereas in mice the growth plate remains open while these animals continue growing into adulthood ( Emons et al, 2011 ; Chagin and Newton, 2019 ). Accordingly, findings on mice must be applied to humans only with care.…”

Section: Skeletal Stem and Progenitor Cells In Developing Bonementioning

confidence: 99%

Niches for Skeletal Stem Cells of Mesenchymal Origin

Kurenkova

Medvedeva

Newton

et al. 2020

Front. Cell Dev. Biol.

Self Cite

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With very few exceptions, all adult tissues in mammals are maintained and can be renewed by stem cells that self-renew and generate the committed progeny required. These functions are regulated by a specific and in many ways unique microenvironment in stem cell niches. In most cases disruption of an adult stem cell niche leads to depletion of stem cells, followed by impairment of the ability of the tissue in question to maintain its functions. The presence of stem cells, often referred to as mesenchymal stem cells (MSCs) or multipotent bone marrow stromal cells (BMSCs), in the adult skeleton has long been realized. In recent years there has been exceptional progress in identifying and characterizing BMSCs in terms of their capacity to generate specific types of skeletal cells in vivo . Such BMSCs are often referred to as skeletal stem cells (SSCs) or skeletal stem and progenitor cells (SSPCs), with the latter term being used throughout this review. SSPCs have been detected in the bone marrow, periosteum, and growth plate and characterized in vivo on the basis of various genetic markers (i.e., Nestin, Leptin receptor, Gremlin1, Cathepsin-K, etc.). However, the niches in which these cells reside have received less attention. Here, we summarize the current scientific literature on stem cell niches for the SSPCs identified so far and discuss potential factors and environmental cues of importance in these niches in vivo . In this context we focus on (i) articular cartilage, (ii) growth plate cartilage, (iii) periosteum, (iv) the adult endosteal compartment, and (v) the developing endosteal compartment, in that order.

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Postnatal skeletal growth is driven by the epiphyseal stem cell niche: potential implications to pediatrics

Cited by 31 publications

References 48 publications

The YAP/TAZ Pathway in Osteogenesis and Bone Sarcoma Pathogenesis

The YAP/TAZ Pathway in Osteogenesis and Bone Sarcoma Pathogenesis

Rickets in Children: An Update

Niches for Skeletal Stem Cells of Mesenchymal Origin

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