IVD Development: Nucleus Pulposus Development and Sclerotome Specification

Alkhatib, Bashar; Ban, Ga I; Williams, Sade; Serra, Rosa

doi:10.1007/s40610-018-0100-3

Cited by 23 publications

(41 citation statements)

References 87 publications

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“…In the fourth week of human gestation, the cells in the sclerotome migrate toward the notochord, giving rise to the formation of two regions of packed cells, one cranially and one caudally. The cell-free space between the two regions is then filled by cells migrating from the caudal cell-packed area, which forms the annulus fibrosus, whereas the nucleus pulposus develops from notochordal material [105,106]. The appearance and progress of the intervertebral disc forces the cell-packed regions of the adjacent somites to interact, leading to the development of the centrum, and later of the vertebral body (Figure 11) [100,106].…”

Section: Embryology and Development Of The Spinementioning

confidence: 99%

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The Spine: A Strong, Stable, and Flexible Structure with Biomimetics Potential

Galbusera

Bassani

2019

Biomimetics

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From its first appearance in early vertebrates, the spine evolved the function of protecting the spinal cord, avoiding excessive straining during body motion. Its stiffness and strength provided the basis for the development of the axial skeleton as the mechanical support of later animals, especially those which moved to the terrestrial environment where gravity loads are not alleviated by the buoyant force of water. In tetrapods, the functions of the spine can be summarized as follows: protecting the spinal cord; supporting the weight of the body, transmitting it to the ground through the limbs; allowing the motion of the trunk, through to its flexibility; providing robust origins and insertions to the muscles of trunk and limbs. This narrative review provides a brief perspective on the development of the spine in vertebrates, first from an evolutionary, and then from an embryological point of view. The paper describes functions and the shape of the spine throughout the whole evolution of vertebrates and vertebrate embryos, from primordial jawless fish to extant animals such as birds and humans, highlighting its fundamental features such as strength, stability, and flexibility, which gives it huge potential as a basis for bio-inspired technologies.

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Section: Embryology and Development Of The Spinementioning

confidence: 99%

“…NT: neural tube; SC: sclerotome; NC: notochord; VB: vertebral body; IVD: intervertebral disc; NP: nucleus pulposus; iAF: inner annulus fibrosus; oAF: outer annulus fibrosus; CEP: cartilaginous endplate. Reprinted with permission from Reference [106].…”

Section: Figurementioning

confidence: 99%

The Spine: A Strong, Stable, and Flexible Structure with Biomimetics Potential

Galbusera

Bassani

2019

Biomimetics

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“…The vertebrate axial skeleton was an evolutionary development that provided support for the body and protection of the spinal cord (Alkhatib, 2018; Cox, 2014). The spine consists of two major components, the bony vertebrae derived from cartilage models through endochondral bone formation and fibrous connective tissues including the intervertebral discs (IVDs), ligaments and tendons.…”

Section: Introductionmentioning

confidence: 99%

Development of the axial skeleton and intervertebral disc

Williams

Alkhatib

Serra

2019

Current Topics in Developmental Biology

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Development of the axial skeleton is a complex, stepwise process that relies on intricate signaling and coordinated cellular differentiation. Disruptions to this process can result in a myriad of skeletal malformations that range in severity. The notochord and the sclerotome are embryonic tissues that give rise to the major components of the intervertebral discs and the vertebral bodies of the spinal column. Through a number of mouse models and characterization of congenital abnormalities in human patients, various growth factors, transcription factors, and other signaling proteins have been demonstrated to have critical roles in the development of the axial skeleton. Balance between opposing growth factors as well as other environmental cues allows for cell fate specification and divergence of tissue types during development. Furthermore, characterization of progenitor cells for specific cell lineages has furthered the understanding of specific spatiotemporal cues that cells need in order to initiate and complete development of distinct tissues. Identifying specific marker genes that can distinguish between the various embryonic and mature cell types is also of importance. Clinically, understanding developmental clues can aid in the generation of therapeutics for musculoskeletal disease through the process of developmental engineering. Studies into potential stem cell therapies are based on knowledge of the normal processes that occur in the embryo, which can then be applied to stepwise tissue engineering strategies.

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“…Differentiation of sclerotome into various components of the axial skeleton, whether cartilaginous or fibrous, is determined by the location of the cells within the embryo and a complex interaction of growth factors. [6,7] Transforming Growth Factor Beta (TGFβ) and Bone Morphogenic Protein (BMP) are important factors that regulate development and cell fate decisions. TGFβ binds to serine/ threonine kinase receptors on the cell surface and transfers signals through transcription factors Smad2 and Smad3.…”

Section: Introductionmentioning

confidence: 99%

Antagonism of BMP signaling is insufficient to induce fibrous differentiation in primary sclerotome

Ban

Williams

Serra

2019

Experimental Cell Research

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Sclerotome is the embryonic progenitor of the axial skeleton. It was previously shown that Tgfbr2 is required in sclerotome for differentiation of fibrous skeletal tissues including the annulus fibrosus of the intervertebral disc. Alternatively, BMP signaling is required to form the vertebral body through chondrogenesis. In addition, TGFβ added to sclerotome cultures induces expression of markers for fibrous tissue differentiation but not cartilage or bone. The mechanism of how TGFβ signaling regulates this lineage decision in sclerotome is not known and could be due to the production of instructive or inhibitory signals or a combination of the two. Here we show that TGFβ antagonizes BMP/ Smad1/5 signaling in primary sclerotome likely through regulation of Noggin, an extracellular BMP antagonist, to prevent chondrogenesis. We then tested whether inhibition of BMP signaling, and inhibition of chondrogenesis, is sufficient to push cells toward the fibrous cell fate. While Noggin inhibited BMP/ Smad1/5 signaling and the formation of chondrogenic nodules in sclerotome cultures; Noggin and inhibition of BMP signaling through Gremlin or DMH2 were insufficient to induce fibrous tissue differentiation. The results suggest inhibition of BMP signaling is not sufficient to stimulate fibrous tissue differentiation and additional signals are likely required. We propose that TGFβ has a dual role in regulating sclerotome fate. First, it inhibits BMP signaling potentially through Noggin to prevent chondrogenesis and, second, it provides an unknown instructive signal to promote fibrous tissue differentiation in sclerotome. The results have implications for the design of stem cell-based therapies for skeletal diseases.

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IVD Development: Nucleus Pulposus Development and Sclerotome Specification

Cited by 23 publications

References 87 publications

The Spine: A Strong, Stable, and Flexible Structure with Biomimetics Potential

The Spine: A Strong, Stable, and Flexible Structure with Biomimetics Potential

Development of the axial skeleton and intervertebral disc

Antagonism of BMP signaling is insufficient to induce fibrous differentiation in primary sclerotome

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