The role of extracellular matrix elasticity and composition in regulating the nucleus pulposus cell phenotype in the intervertebral disc: a narrative review.

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2014-02

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Abstract

Intervertebral disc (IVD) disorders are a major contributor to disability and societal health care costs. Nucleus pulposus (NP) cells of the IVD exhibit changes in both phenotype and morphology with aging-related IVD degeneration that may impact the onset and progression of IVD pathology. Studies have demonstrated that immature NP cell interactions with their extracellular matrix (ECM) may be key regulators of cellular phenotype, metabolism and morphology. The objective of this article is to review our recent experience with studies of NP cell-ECM interactions that reveal how ECM cues can be manipulated to promote an immature NP cell phenotype and morphology. Findings demonstrate the importance of a soft (<700 Pa), laminin-containing ECM in regulating healthy, immature NP cells. Knowledge of NP cell-ECM interactions can be used for development of tissue engineering or cell delivery strategies to treat IVD-related disorders.

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10.1115/1.4026360

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Hwang, Priscilla Y, Jun Chen, Liufang Jing, Brenton D Hoffman and Lori A Setton (2014). The role of extracellular matrix elasticity and composition in regulating the nucleus pulposus cell phenotype in the intervertebral disc: a narrative review. J Biomech Eng, 136(2). p. 021010. 10.1115/1.4026360 Retrieved from https://hdl.handle.net/10161/8879.

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Hoffman

Brenton D. Hoffman

James L. and Elizabeth M. Vincent Associate Professor of Biomedical Engineering

The overall goal of my research program is to utilize an interdisciplinary approach to first advance the basic understanding of mechanotransduction on multiple scales and then use this knowledge to guide the development of new treatments for mechanosensitive diseases. Our work combines principles and techniques from protein engineering, molecular biology, soft matter physics, cell and developmental biology, biomaterials engineering, automated image analysis, and state of the art live cell microscopy. Specifically, we engineer and use biosensors that report the tension across specific proteins in living cells through changes in the color of light they emit. This technology enables dynamic measurements of proteins and sub-cellular structures that are under load. Unlike more traditional techniques that measure the entirety of cellular force output, the ability of these sensors to measure mechanical stress at the molecular level means they are innately compatible with concepts and approaches common in molecular biology and biophysics.


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