title: Severe Spinal Cord Injury Causes Immediate Multi-cellular Dysfunction at the Chondro-Osseous Junction.
abstract: Spinal cord injury is associated with rapid bone loss and arrested long bone growth due to mechanisms that are poorly understood. In this study, we sought to determine the effects of severe T10 contusion spinal cord injury on the sublesional bone microenvironment in adolescent rats. A severe lower thoracic (vertebral T10) spinal cord injury was generated by weight drop (10 g×50 mm). Severely injured and body weight-matched uninjured male Sprague-Dawley rats were studied. At 3 and 5 days post-injury, we performed histological analysis of the distal femoral metaphysis, TUNEL assay, immunohistochemistry, real-time PCR, and western blot analysis compared to uninjured controls. We observed severe hindlimb functional deficits typical of this model. We detected uncoupled remodeling with increased osteoclast activity in the absence of osteoblast activity. We detected osteoblast, osteocyte, and chondrocyte apoptosis with suppressed osteoblast and chondrocyte proliferation and growth plate arrest due to spinal cord injury. We also detected altered gene expression in both whole bone extracts and bone marrow monocytes following spinal cord injury. We conclude that spinal cord injury results in altered gene expression of key regulators of osteoblast and chondrocyte activity. This leads to premature cellular apoptosis, suppressed cellular proliferation, growth plate arrest, and uncoupled bone remodeling in sublesional bone with unopposed osteoclastic resorption.
authors.affiliation: Spaulding-Harvard Spinal Cord Injury Model System, Spaulding Rehabilitation Hospital, Boston, MA, USA. Department of Cytokine Biology, Forsyth Institute, Boston, MA, USA. Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA, USA. Department of PMR, Harvard Medical School, The Forsyth Institute, 140 The Fenway, Boston, MA 02118, USA.
authors.forename: Leslie R
authors.initials: LR
authors.lastname: Morse
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Bethlehem
authors.initials: B
authors.lastname: Solomon
authors.forename: Lara
authors.initials: L
authors.lastname: Boyle
authors.forename: Subbiah
authors.initials: S
authors.lastname: Yoganathan
authors.forename: Philip
authors.initials: P
authors.lastname: Stashenko
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Battaglino