title: Increased lubricin/proteoglycan 4 gene expression and decreased modulus in medial collateral ligaments following ovariohysterectomy in the adult rabbit: Evidence consistent with aging.
abstract: This study investigated whether ovariohysterectomy (OVH) surgery to induce menopause resulted in changes to modulus, failure strain and lubricin/proteoglycan 4 (PRG4) gene expression in rabbit medial collateral ligaments (MCLs), similar to aging (Thornton et al., 2015a). The MCLs from adult rabbits that underwent OVH surgery as adolescents (15-week-old) and adults (1-year-old) were compared by evaluating mechanical behaviour (adolescent OVH, n=8; adult OVH, n=7; normal, n=7), gene expression (adolescent OVH, n=9; adult OVH, n=8; normal, n=8), and collagen and glycosaminoglycan (adolescent OVH, n=9; adult OVH, n=8; normal, n=8) and water (adolescent OVH, n=9; adult OVH, n=8; normal, n=8) content. Mechanical behaviour evaluated cyclic, static and total creep strain, and ultimate tensile strength, modulus and failure strain. The RT-qPCR assessed mRNA levels for matrix regulatory genes. Adult OVH MCLs exhibited increased cyclic creep and failure strain, and decreased modulus with increased mRNA levels for lubricin/PRG4 and collagen I compared with normal MCLs. Adolescent OVH MCLs exhibited increased cyclic, static and total creep strain with decreased mRNA levels for the progesterone receptor. Lubricin/PRG4 plays a role in the lubrication of collagen fascicles which is likely related to the decreased modulus and increased failure strain observed in ligaments from adult OVH rabbits. Progesterone and its receptor are thought to play a role in the stretching of ligaments in pelvic organ prolapse and pregnancy which is likely related to the increase in creep strain observed in ligaments from adolescent OVH rabbits. Ovariohysterectomy in adult rabbits resulted in changes that were consistent with the aging MCL.
authors.affiliation: McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Devin B
authors.initials: DB
authors.lastname: Lemmex
authors.affiliation: McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, Alberta, Canada; Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Ono
authors.affiliation: McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Carol R
authors.initials: CR
authors.lastname: Reno
authors.affiliation: McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, Alberta, Canada.
authors.forename: David A
authors.initials: DA
authors.lastname: Hart
authors.affiliation: McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Ian K Y
authors.initials: IK
authors.lastname: Lo
authors.affiliation: McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, Alberta, Canada; Department of Orthopaedics, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: gail.thornton@ucalgary.ca.
authors.forename: Gail M
authors.initials: GM
authors.lastname: Thornton
mesh_terms: D000375:Aging; D000818:Animals; D001696:Biomechanical Phenomena; D003094:Collagen / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007044:Hysterectomy; D017888:Medial Collateral Ligament, Knee / Q000378:metabolism* / Q000503:physiopathology; D008593:Menopause; D010052:Ovariectomy; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D011817:Rabbits; D015533:Transcriptional Activation; D015854:Up-Regulation; D000099158:Proteoglycan 4
chemical_list: D003094:Collagen; D006023:Glycoproteins; D011509:Proteoglycans; D000099158:Proteoglycan 4
keywords: Creep; Ligament; Lubricin/Proteoglycan 4; Menopause; Modulus; Progesterone Receptor; Strain