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Elastogenic protein expression of a highly elastic murine spinal ligament: the ligamentum flavum.

Brown JP, Lind RM, Burzesi AF, Kuo CK - PLoS ONE (2012)

Bottom Line: We found that elastogenesis begins in utero with the microfibril constituent fibrillin-1 staining intensely just before birth.These expression patterns correlated with reported skeletal and behavioral changes during murine development.This immunohistochemical characterization of elastogenesis of the LF will be useful for future studies investigating mechanisms for elastogenesis and developing new strategies for treatment or regeneration of spinal ligaments and other highly elastic tissues.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Tufts University, Medford, Massachusetts, United States of America.

ABSTRACT
Spinal ligaments, such as the ligamentum flavum (LF), are prone to degeneration and iatrogenic injury that can lead to back pain and nerve dysfunction. Repair and regeneration strategies for these tissues are lacking, perhaps due to limited understanding of spinal ligament formation, the elaboration of its elastic fibers, maturation and homeostasis. Using immunohistochemistry and histology, we investigated murine LF elastogenesis and tissue formation from embryonic to mature postnatal stages. We characterized the spatiotemporal distribution of the key elastogenic proteins tropoelastin, fibrillin-1, fibulin-4 and lysyl oxidase. We found that elastogenesis begins in utero with the microfibril constituent fibrillin-1 staining intensely just before birth. Elastic fibers were first detected histologically at postnatal day (P) 7, the earliest stage at which tropoelastin and fibulin-4 stained intensely. From P7 to P28, elastic fibers grew in diameter and became straighter along the axis. The growth of elastic fibers coincided with intense staining of tropoelastin and fibulin-4 staining, possibly supporting a chaperone role for fibulin-4. These expression patterns correlated with reported skeletal and behavioral changes during murine development. This immunohistochemical characterization of elastogenesis of the LF will be useful for future studies investigating mechanisms for elastogenesis and developing new strategies for treatment or regeneration of spinal ligaments and other highly elastic tissues.

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Timeline summarizing elastogenesis in LF during development, maturation and aging.Timeline summarizing elastogenic protein expression in the LF; stages/ages are in days unless otherwise indicated. Not drawn to scale.
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pone-0038475-g008: Timeline summarizing elastogenesis in LF during development, maturation and aging.Timeline summarizing elastogenic protein expression in the LF; stages/ages are in days unless otherwise indicated. Not drawn to scale.

Mentions: Spinal ligaments are prone to various forms of degeneration that can lead to back pain and nerve dysfunction. Some spinal ligaments, such as the LF, are highly elastic. Little is known about how the LF develops beyond the observations that the embryonic LF is more cellular and has fewer elastic fibers than does adult LF [28], [29], which our data corroborates. Knowledge of the formation, homeostasis, and degeneration of the LF may enhance the development of repair and regeneration strategies for the LF. Toward that end, this study characterized spatiotemporal distribution of elastogenic proteins during LF development, maturation and aging (summarized in Fig. 8).


Elastogenic protein expression of a highly elastic murine spinal ligament: the ligamentum flavum.

Brown JP, Lind RM, Burzesi AF, Kuo CK - PLoS ONE (2012)

Timeline summarizing elastogenesis in LF during development, maturation and aging.Timeline summarizing elastogenic protein expression in the LF; stages/ages are in days unless otherwise indicated. Not drawn to scale.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3369910&req=5

pone-0038475-g008: Timeline summarizing elastogenesis in LF during development, maturation and aging.Timeline summarizing elastogenic protein expression in the LF; stages/ages are in days unless otherwise indicated. Not drawn to scale.
Mentions: Spinal ligaments are prone to various forms of degeneration that can lead to back pain and nerve dysfunction. Some spinal ligaments, such as the LF, are highly elastic. Little is known about how the LF develops beyond the observations that the embryonic LF is more cellular and has fewer elastic fibers than does adult LF [28], [29], which our data corroborates. Knowledge of the formation, homeostasis, and degeneration of the LF may enhance the development of repair and regeneration strategies for the LF. Toward that end, this study characterized spatiotemporal distribution of elastogenic proteins during LF development, maturation and aging (summarized in Fig. 8).

Bottom Line: We found that elastogenesis begins in utero with the microfibril constituent fibrillin-1 staining intensely just before birth.These expression patterns correlated with reported skeletal and behavioral changes during murine development.This immunohistochemical characterization of elastogenesis of the LF will be useful for future studies investigating mechanisms for elastogenesis and developing new strategies for treatment or regeneration of spinal ligaments and other highly elastic tissues.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Tufts University, Medford, Massachusetts, United States of America.

ABSTRACT
Spinal ligaments, such as the ligamentum flavum (LF), are prone to degeneration and iatrogenic injury that can lead to back pain and nerve dysfunction. Repair and regeneration strategies for these tissues are lacking, perhaps due to limited understanding of spinal ligament formation, the elaboration of its elastic fibers, maturation and homeostasis. Using immunohistochemistry and histology, we investigated murine LF elastogenesis and tissue formation from embryonic to mature postnatal stages. We characterized the spatiotemporal distribution of the key elastogenic proteins tropoelastin, fibrillin-1, fibulin-4 and lysyl oxidase. We found that elastogenesis begins in utero with the microfibril constituent fibrillin-1 staining intensely just before birth. Elastic fibers were first detected histologically at postnatal day (P) 7, the earliest stage at which tropoelastin and fibulin-4 stained intensely. From P7 to P28, elastic fibers grew in diameter and became straighter along the axis. The growth of elastic fibers coincided with intense staining of tropoelastin and fibulin-4 staining, possibly supporting a chaperone role for fibulin-4. These expression patterns correlated with reported skeletal and behavioral changes during murine development. This immunohistochemical characterization of elastogenesis of the LF will be useful for future studies investigating mechanisms for elastogenesis and developing new strategies for treatment or regeneration of spinal ligaments and other highly elastic tissues.

Show MeSH
Related in: MedlinePlus