Title | The aging mouse partially models the aging human spine: lumbar and coccygeal disc height, composition, mechanical properties, and Wnt signaling in young and old mice. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Holguin N, Aguilar R, Harland RA, Bomar BA, Silva MJ |
Journal | J Appl Physiol (1985) |
Volume | 116 |
Issue | 12 |
Pagination | 1551-60 |
Date Published | 2014 Jun 15 |
ISSN | 1522-1601 |
Keywords | Aging, Animals, Collagen, Female, Glycosaminoglycans, Humans, Intervertebral Disc, Lumbar Vertebrae, Mice, Mice, Inbred C57BL, Wnt Signaling Pathway |
Abstract | Murine lumbar and coccygeal (tail) regions of spines are commonly used to study cellular signaling of age-related disc diseases, but the tissue-level changes of aging intervertebral discs and vertebrae of each spinal region remain unclear. Furthermore, the impact of aging lumbar and coccygeal discs on Wnt/β-catenin signaling, which is putatively involved in the catabolism of intervertebral discs, is also unclear. We compared disc/vertebrae morphology and mechanics and biochemical composition of intervertebral discs from lumbar and coccygeal regions between young (4-5 mo) and old (20-22 mo) female C57BL/6 mice. Center intervertebral disc height from both regions was greater in old discs than young discs. Compared with young, old lumbar discs had a lower early viscous coefficient (a measure of stiffness) by 40%, while conversely old coccygeal discs were stiffer by 53%. Biochemically, old mice had double the collagen content in lumbar and coccygeal discs of young discs, greater glycosaminoglycan in lumbar discs by 37%, but less glycosaminoglycan in coccygeal discs by 32%. Next, we compared Wnt activity of lumbar and coccygeal discs of 4- to 5-mo and 12- to 14-mo TOPGAL mice. Despite the disc-specific changes, aging decreased Wnt signaling in the nucleus pulposus from both spinal regions by ≥64%. Compared with young, trabecular bone volume/tissue volume and ultimate force were less in old lumbar vertebrae, but greater in old coccygeal vertebrae. Thus intervertebral discs and vertebrae age in a spinal region-dependent manner, but these differential age-related changes may be uncoupled from Wnt signaling. Overall, lumbar and coccygeal regions are not interchangeable in modeling human aging. |
DOI | 10.1152/japplphysiol.01322.2013 |
Alternate Journal | J. Appl. Physiol. |
PubMed ID | 24790018 |
PubMed Central ID | PMC4064379 |
Grant List | S10 RR023660 / RR / NCRR NIH HHS / United States R01 AR-047867 / AR / NIAMS NIH HHS / United States P30 AR-057235 / AR / NIAMS NIH HHS / United States R01 AR047867 / AR / NIAMS NIH HHS / United States T32 AR060719 / AR / NIAMS NIH HHS / United States T32 AR-060719 / AR / NIAMS NIH HHS / United States P30 AR057235 / AR / NIAMS NIH HHS / United States |
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