title: Biological responses to flexion/extension in spinal segments ex-vivo.
abstract: Mechanical loading is a salient factor in the progression of spinal disorders that contribute to back pain. Biological responses to loading modes like flexion/extension (F/E) in relevant spinal tissues remain unstudied. A novel, multi-axial experimental system was developed to subject viable functional spinal units (FSUs) to complex, in-situ loading. The objective was to determine biological effects of F/E in multiple spinal tissues-annulus fibrosus, nucleus pulposus, facet cartilage, and ligamentum flavum. Rabbit lumbar FSUs were mounted in a bioreactor within a robotic testing system. FSUs underwent small (0.17/0.05 Nm) and large (0.5/0.15 Nm) range-of-motion F/E for 1 or 2 h of cycling. Outcomes in each tissue, compared to unloaded FSUs, included (i) relative mRNA expression of catabolic (MMP-1, 3 and ADAMTS-5), pro-inflammatory (COX-2), and anabolic (ACAN) genes and (ii) immunoblotting of aggrecan degradation. Total energy applied to FSUs increased in groups subject to large range-of-motion and 2-h cycling, and moment relaxation was higher with large range-of-motion. F/E significantly modulated MMP1,-3 and COX-2 in facet cartilage and MMP-3 and ACAN in annulus fibrosus. Large range-of-motion loading increased MMP-mediated aggrecan fragmentation in annulus fibrosus. Biological responses to complex loading ex vivo showed variation among spinal tissues that reflect tissue structure and mechanical loading in F/E.
authors: Department of Physical Medicine and Rehabilitation, University of Pittsburgh, 3471 5th Avenue, Pittsburgh, Pennsylvania, 15213.|Department of Bioengineering, University of Pittsburgh, 300 Technology Drive, 360B Center for Bioengineering, Pittsburgh, Pennsylvania, 15219.
authors: Robert A
authors: RA
authors: Hartman
authors: Department of Orthopaedic Surgery, University of Pittsburgh, 200 Lothrop Street, E1641 Biomedical Science Tower, Pittsburgh, Pennsylvania, 15261.
authors: Takashi
authors: T
authors: Yurube
authors: Department of Orthopaedic Surgery, University of Pittsburgh, 200 Lothrop Street, E1641 Biomedical Science Tower, Pittsburgh, Pennsylvania, 15261.
authors: Kevin
authors: K
authors: Ngo
authors: Department of Orthopaedic Surgery, University of Pittsburgh, 200 Lothrop Street, E1641 Biomedical Science Tower, Pittsburgh, Pennsylvania, 15261.
authors: Nicolas E
authors: NE
authors: Merzlak
authors: Department of Bioengineering, University of Pittsburgh, 300 Technology Drive, 360B Center for Bioengineering, Pittsburgh, Pennsylvania, 15219.|Department of Orthopaedic Surgery, University of Pittsburgh, 200 Lothrop Street, E1641 Biomedical Science Tower, Pittsburgh, Pennsylvania, 15261.
authors: Richard E
authors: RE
authors: Debski
authors: Department of Bioengineering, University of Pittsburgh, 300 Technology Drive, 360B Center for Bioengineering, Pittsburgh, Pennsylvania, 15219.|McGowan Institute for Regenerative Medicine, 450 Technology Drive, Suite 300, Pittsburgh, Pennsylvania, 15219.
authors: Bryan N
authors: BN
authors: Brown
authors: Department of Orthopaedic Surgery, University of Pittsburgh, 200 Lothrop Street, E1641 Biomedical Science Tower, Pittsburgh, Pennsylvania, 15261.
authors: James D
authors: JD
authors: Kang
authors: Department of Physical Medicine and Rehabilitation, University of Pittsburgh, 3471 5th Avenue, Pittsburgh, Pennsylvania, 15213.|Department of Bioengineering, University of Pittsburgh, 300 Technology Drive, 360B Center for Bioengineering, Pittsburgh, Pennsylvania, 15219.|Department of Orthopaedic Surgery, University of Pittsburgh, 200 Lothrop Street, E1641 Biomedical Science Tower, Pittsburgh, Pennsylvania, 15261.
authors: Gwendolyn A
authors: GA
authors: Sowa
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D051546:Cyclooxygenase 2 / Q000502:physiology; D007403:Intervertebral Disc / Q000502:physiology; D017843:Ligamentum Flavum / Q000502:physiology; D008159:Lumbar Vertebrae / Q000502:physiology*; D019278:Matrix Metalloproteinase 3 / Q000502:physiology; D011817:Rabbits; D016059:Range of Motion, Articular
chemical_list: D051546:Cyclooxygenase 2; D019278:Matrix Metalloproteinase 3
keywords: facet cartilage; flexion/extension; intervertebral disc; ligamentum flavum; mechanobiology