title: Sex differences in tendon structure and function.
abstract: Tendons play a critical role in the transmission of forces between muscles and bones, and chronic tendon injuries and diseases are among the leading causes of musculoskeletal disability. Little is known about sex-based differences in tendon structure and function. Our objective was to evaluate the mechanical properties, biochemical composition, transcriptome, and cellular activity of plantarflexor tendons from 4 month old male and female C57BL/6 mice using in vitro biomechanics, mass spectrometry-based proteomics, genome-wide expression profiling, and cell culture techniques. While the Achilles tendons of male mice were approximately 6% larger than female mice (p < 0.05), the cell density of female mice was around 19% greater than males (p < 0.05). No significant differences in mechanical properties (p > 0.05) of plantaris tendons were observed. Mass spectrometry proteomics analysis revealed no significant difference between sexes in the abundance of major extracellular matrix (ECM) proteins such as collagen types I (p = 0.30) and III (p = 0.68), but female mice had approximately twofold elevations (p < 0.05) in less abundant ECM proteins such as fibronectin, periostin, and tenascin C. The transcriptome of male and female tendons differed by only 1%. In vitro, neither the sex of the serum that fibroblasts were cultured in, nor the sex of the ECM in which they were embedded, had profound effects on the expression of collagen and cell proliferation genes. Our results indicate that while male mice expectedly had larger tendons, male and female tendons have very similar mechanical properties and biochemical composition, with small increases in some ECM proteins and proteoglycans evident in female tendons. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2117-2126, 2017.
authors.affiliation: Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Dylan C
authors.initials: DC
authors.lastname: Sarver
authors.affiliation: Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Yalda Ashraf
authors.initials: YA
authors.lastname: Kharaz
authors.affiliation: Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, Michigan.|Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan.|Department of Surgery, Section of Plastic Surgery, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Kristoffer B
authors.initials: KB
authors.lastname: Sugg
authors.affiliation: Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, Michigan.|Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Gumucio
authors.affiliation: Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Eithne
authors.initials: E
authors.lastname: Comerford
authors.affiliation: Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, Michigan.|Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Mendias
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D005109:Extracellular Matrix / Q000502:physiology; D005260:Female; D005347:Fibroblasts / Q000502:physiology; D008297:Male; D008810:Mice, Inbred C57BL; D012727:Sex Characteristics; D013710:Tendons / Q000033:anatomy & histology* / Q000502:physiology*; D059467:Transcriptome
keywords: mechanics; proteomics; sex; tendon; transcriptomics