Decreased physical function and increased pain sensitivity in mice deficient for type IX collagen.

Decreased physical function and increased pain sensitivity in mice deficient for type IX collagen.
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DOI:
10.1002/art.24783
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发表时间:
2009-09
影响因子:
--
通讯作者:
Setton, Lori A.
Setton, Lori A.
中科院分区:
其他
文献类型:
--
作者:
Allen, Kyle D.;Griffin, Timothy M.;Rodriguiz, Ramona M.;Wetsel, William C.;Kraus, Virginia B.;Huebner, Janet L.;Boyd, Lawrence M.;Setton, Lori A.

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Mice with Col9a1 gene inactivation (Col9a1-/-) prematurely develop osteoarthritis and intervertebral disc degeneration. In this study, we investigate Col9a1-/- mice for functional and symptomatic changes that may associate with these pathologies. Col9a1-/- and wildtype mice were investigated for reflexes, functional impairments, (beam walking, pole climbing, wire-hang, grip-strength), sensorimotor skills (rotarod), mechanical sensitivity (von Frey hair) and thermal sensitivity (hot plate/tail flick). Gait was also analyzed to determine velocity, stride frequency, symmetry, percentage stance times, stride lengths, and step widths. Post-mortem, serum was analyzed for hyaluronan, and knees and spines were graded histologically for degeneration. Col9a1-/- mice had compensatory gait changes, increased mechanical sensitivity, and impaired physical ability. Col9a1-/- mice ambulated with gaits characterized by increased percentage stance times and shorter stride lengths. These mice also had heightened mechanical sensitivity and were deficient in contact righting, wire-hang, rotarod, and pole climbing. Male-Col9a1-/- mice had the highest mean serum hyaluronan levels and strong histological evidence of cartilage erosion. Intervertebral disc degeneration was also detected, with Col9a1-/- mice having increased incidence of disc tears. These data describe a Col9a1-/- behavioral phenotype characterized by altered gait, increased mechanical sensitivity, and impaired function. These gait and functional differences suggest Col9a1-/- mice select locomotive behaviors that limit joint loads. The nature and magnitude of behavioral changes were largest in males, which also had the greatest evidence of knee degeneration. These findings suggest that Col9a1-/- mice present behavioral changes consistent with anatomic signs of osteoarthritis and intervertebral disc degeneration.
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