Integrin-mediated interactions with extracellular matrix proteins for nucleus pulposus cells of the human intervertebral disc.
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The extracellular matrix (ECM) of the human intervertebral disc is rich in molecules that interact with cells through integrin-mediated attachments. Porcine nucleus pulposus (NP) cells have been shown to interact with laminin (LM) isoforms LM-111 and LM-511 through select integrins that regulate biosynthesis and cell attachment. Since human NP cells lose many phenotypic characteristics with age, attachment and interaction with the ECM may be altered. Expression of LM-binding integrins was quantified for human NP cells using flow cytometry. The cell-ECM attachment mechanism was determined by quantifying cell attachment to LM-111, LM-511, or type II collagen after functionally blocking specific integrin subunits. Human NP cells express integrins β1, α3, and α5, with over 70% of cells positive for each subunit. Blocking subunit β1 inhibited NP cell attachment to all substrates. Blocking subunits α1, α2, α3, and α5 simultaneously, but not individually, inhibits NP cell attachment to laminins. While integrin α6β1 mediated porcine NP cell attachment to LM-111, we found integrins α3, α5, and β1 instead contributed to human NP cell attachment. These findings identify integrin subunits that may mediate interactions with the ECM for human NP cells and could be used to promote cell attachment, survival, and biosynthesis in cell-based therapeutics.
nucleus pulposus, integrin
Extracellular Matrix Proteins
Intervertebral Disc Displacement
Published Version (Please cite this version)10.1002/jor.22395
Publication InfoBridgen, DT; Brown, CR; Chen, J; Gilchrist, CL; Isaacs, RE; Richardson, William J; ... Yang, KL (2013). Integrin-mediated interactions with extracellular matrix proteins for nucleus pulposus cells of the human intervertebral disc. J Orthop Res, 31(10). pp. 1661-1667. 10.1002/jor.22395. Retrieved from http://hdl.handle.net/10161/7860.
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Professor of Orthopaedic Surgery
1. Current research includes investigation of biomechanical aspects of cervical injury with head impact. This involves cadaveric work with high-speed photography and load cells to ascertain the mechanism for spinal fractures. 2. An animal model is being used to evaluate the biomechanics of cervical laminectomy versus laminoplasty compared to the normal spine. A portion of the animals are developing myelopathy secondary to instability after the surgical procedure and this is bei
Adjunct Professor of Biomedical Engineering
Research in Setton's laboratory is focused on the role of mechanical factors in the degeneration and repair of soft tissues of the musculoskeletal system, including the intervertebral disc, articular cartilage and meniscus. Work in the Laboratory is focused on engineering and evaluating materials for tissue regeneration and drug delivery. Studies combining engineering and biology are also used to determine the role of mechanical factors to promote and control healing of cartilaginous tissues. Re
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Regulation of Human Nucleus Pulposus Cell Phenotype and Behavior by Laminin-Mimetic Peptide Substrates Bridgen, Devin (2015)Intervertebral disc (IVD) disorders can cause pain and disability for affected individuals. A subset of IVD disorders are thought to originate in the nucleus pulposus (NP) region of the IVD, due to alterations in tissue ...