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.

TitleThe 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 TypeJournal Article
Year of Publication2014
AuthorsHolguin N, Aguilar R, Harland RA, Bomar BA, Silva MJ
JournalJ Appl Physiol (1985)
Volume116
Issue12
Pagination1551-60
Date Published2014 Jun 15
ISSN1522-1601
KeywordsAging, 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.

DOI10.1152/japplphysiol.01322.2013
Alternate JournalJ. Appl. Physiol.
PubMed ID24790018
PubMed Central IDPMC4064379
Grant ListS10 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