title: Lubricin deficiency in the murine lumbar intervertebral disc results in elevated torsional apparent modulus.
abstract: The purpose of this study was to investigate the mechanical consequences of proteoglycan 4 (Prg4) deficiency on intervertebral disc mechanics using a Prg4 knockout mouse model. Prg4, also called lubricin, was first identified as the boundary lubricant in synovial fluid but has subsequently been localized within a number of musculoskeletal tissues in areas subjected to shear and tensile stresses, including the intervertebral disc. The function of lubricin in the intervertebral disc has not been determined. Lumbar level 1-2 vertebral body-disc-vertebral body motion segments were isolated from Prg4 null mice and wild type (WT) litter mate controls. Disc dimensions were measured and motion segments were tested in axial loading and torsion. Torque measurements and disc dimensions were used to calculate the torsional apparent modulus for discs from Prg4 null and WT discs. Discs from Prg4 null mice had a significantly smaller mean transverse disc area (p=0.0057), with a significantly larger proportion of this area occupied by the nucleus pulposus (p<0.0001), compared to WT specimens. Apparent torsional moduli were found to be elevated in Prg4 null lumbar discs compared to WT controls at 10-10° (p=0.0048) and 10-30° (p=0.0127) rotation. This study suggests a functional role for Prg4 in the murine intervertebral disc. The absence of Prg4 was associated with an increased apparent torsional modulus and the structural consequences of Prg4 deficiency in the intervertebral disc, with expansion of the area of the nucleus pulposus relative to the transverse disc area in Prg4 null specimens.
authors.affiliation: Department of Occupational and Environmental Medicine, Harvard School of Public Health, Boston, MA, USA; Department of Orthopedic Surgery, Brigham and Women׳s Hospital, OrACORe Group, 75 Francis St, BC-4016, Boston, MA 02115 USA. Electronic address: ert890@mail.harvard.edu.
authors.forename: Erin
authors.initials: E
authors.lastname: Teeple
authors.affiliation: Bioengineering Laboratory, Department of Orthopaedics, Warren Alpert Medical School, Brown University/Rhode Island Hospital, Providence, RI, USA.
authors.forename: Koosha
authors.initials: K
authors.lastname: Aslani
authors.affiliation: Bioengineering Laboratory, Department of Orthopaedics, Warren Alpert Medical School, Brown University/Rhode Island Hospital, Providence, RI, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Shalvoy
authors.affiliation: Bioengineering Laboratory, Department of Orthopaedics, Warren Alpert Medical School, Brown University/Rhode Island Hospital, Providence, RI, USA.
authors.forename: Jade E
authors.initials: JE
authors.lastname: Medrano
authors.affiliation: Department of Emergency Medicine, Rhode Island Hospital, Providence, RI, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Lifespan Biostatistics Core, Lifespan Hospital System, Providence, RI, USA; Departments of Orthopaedics & Surgery, Warren Alpert Medical School, Brown University, Providence, RI, USA.
authors.forename: Jason T
authors.initials: JT
authors.lastname: Machan
authors.affiliation: Bioengineering Laboratory, Department of Orthopaedics, Warren Alpert Medical School, Brown University/Rhode Island Hospital, Providence, RI, USA; School of Engineering, Brown University, Providence, RI, USA.
authors.forename: Braden C
authors.initials: BC
authors.lastname: Fleming
authors.affiliation: Department of Emergency Medicine, Rhode Island Hospital, Providence, RI, USA; School of Engineering, Brown University, Providence, RI, USA.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Jay
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D055119:Elastic Modulus; D007403:Intervertebral Disc / Q000378:metabolism* / Q000502:physiology; D008159:Lumbar Vertebrae / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011509:Proteoglycans / Q000172:deficiency* / Q000235:genetics; D000099158:Proteoglycan 4
chemical_list: D011509:Proteoglycans; C498837:Prg4 protein, mouse; D000099158:Proteoglycan 4
keywords: Apparent torsional modulus; Disc; Lubricin; Prg4; Proteoglycan 4