title: Physiological loading can restore the proteoglycan content in a model of early IVD degeneration.
abstract: A hallmark of early IVD degeneration is a decrease in proteoglycan content. Progression will eventually lead to matrix degradation, a decrease in weight bearing capacity and loss of disc height. In the final stages of IVD degradation, fissures appear in the annular ring allowing extrusion of the NP. It is crucial to understand the interplay between mechanobiology, disc composition and metabolism to be able to provide exercise recommendations to patients with early signs of disc degeneration. This study evaluates the effect of physiological loading compared to no loading on matrix homeostasis in bovine discs with induced degeneration. Bovine discs with trypsin-induced degeneration were cultured for 14 days in a bioreactor under dynamic loading with maintained metabolic activity. Chondroadherin abundance and structure was used to confirm that a functional matrix was preserved in the chosen loading environment. No change was observed in chondroadherin integrity and a non-significant increase in abundance was detected in trypsin-treated loaded discs compared to unloaded discs. The proteoglycan concentration in loaded trypsin-treated discs was significantly higher than in unloaded disc and the newly synthesised proteoglycans were of the same size range as those found in control samples. The proteoglycan showed an even distribution throughout the NP region, similar to that of control discs. Significantly more newly synthesised type II collagen was detected in trypsin-treated loaded discs compared to unloaded discs, demonstrating that physiological load not only stimulates aggrecan production, but also that of type II collagen. Taken together, this study shows that dynamic physiological load has the ability to repair the extracellular matrix depletion typical of early disc degeneration.
authors.affiliation: Orthopaedic Research Laboratory, McGill University, Montreal, Quebec, Canada.
authors.forename: Rahul
authors.initials: R
authors.lastname: Gawri
authors.affiliation: Orthopaedic Research Laboratory, McGill University, Montreal, Quebec, Canada.
authors.forename: Janet
authors.initials: J
authors.lastname: Moir
authors.affiliation: McGill Scoliosis and Spine Group, Montreal, Quebec, Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Ouellet
authors.affiliation: Orthopaedic Research Laboratory, McGill University, Montreal, Quebec, Canada.
authors.forename: Lorne
authors.initials: L
authors.lastname: Beckman
authors.affiliation: Orthopaedic Research Laboratory, McGill University, Montreal, Quebec, Canada.
authors.forename: Thomas
authors.initials: T
authors.lastname: Steffen
authors.affiliation: Shriners Hospital for Children, McGill University, Montreal, Quebec, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Roughley
authors.affiliation: Orthopaedic Research Laboratory, McGill University, Montreal, Quebec, Canada.
authors.forename: Lisbet
authors.initials: L
authors.lastname: Haglund
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D024043:Collagen Type II / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D007403:Intervertebral Disc / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D011312:Pressure; D011509:Proteoglycans / Q000378:metabolism*; D014357:Trypsin / Q000378:metabolism
chemical_list: D024043:Collagen Type II; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; C088980:chondroadherin; D014357:Trypsin