title: The influence of α-actinin-3 deficiency on bone remodelling markers in young men.
abstract: There is a large individual variation in the bone remodelling markers (BRMs) osteocalcin (OC), procollagen 1 N-terminal propeptide (P1NP) and β-isomerized C-terminal telopeptide (β-CTx), as well as undercarboxylated osteocalcin (ucOC), at rest and in response to exercise. α-actinin-3 (ACTN3), a sarcomeric protein, is expressed in skeletal muscle and osteoblasts and may influence BRM levels and the cross-talk between muscle and bone. We tested the levels of serum BRMs in α-actinin-3 deficient humans (ACTN3 XX) at baseline, and following a single bout of exercise. Forty-three healthy Caucasian individuals were divided into three groups (ACTN3 XX, n=13; ACTN3 RX, n=16; ACTN3 RR, n=14). Participants completed a single session of High Intensity Interval Exercise (HIIE) on a cycle ergometer (8×2-min intervals at 85% of maximal power). Blood samples were taken before, immediately after, and three hours post exercise to identify the peak changes in serum BRMs. There was a stepwise increase in resting serum BRMs across the ACTN3 genotypes (XX>RX>RR) with significantly higher levels of tOC ~26%, P1NP ~34%, and β-CTX (~33%) in those with ACTN3 XX compared to ACTN3 RR. Following exercise BRMs and ucOC were higher in all three ACTN3 genotypes, with no significant differences between groups. Serum levels of tOC, P1NP and β-CTX are higher in men with ACTN3 XX genotype (α-actinin-3 deficiency) compared to RR and RX. It appears that the response of BRMs and ucOC to exercise is not explained by the ACTN3 genotype.
authors.affiliation: Institute of Sport, Exercise and Active Living (ISEAL), College of Sport and Exercise Science, Victoria University, Melbourne, Australia. Electronic address: Itamar.Levinger@vu.edu.au.
authors.forename: Itamar
authors.initials: I
authors.lastname: Levinger
authors.affiliation: Institute of Sport, Exercise and Active Living (ISEAL), College of Sport and Exercise Science, Victoria University, Melbourne, Australia; Murdoch Childrens Research Institute, Melbourne, Australia.
authors.forename: Xu
authors.initials: X
authors.lastname: Yan
authors.affiliation: Institute of Sport, Exercise and Active Living (ISEAL), College of Sport and Exercise Science, Victoria University, Melbourne, Australia; School of Medical and Health Sciences, Edith Cowan University, Perth, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Bishop
authors.affiliation: Murdoch Childrens Research Institute, Melbourne, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Houweling
authors.affiliation: Institute of Sport, Exercise and Active Living (ISEAL), College of Sport and Exercise Science, Victoria University, Melbourne, Australia.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Papadimitriou
authors.affiliation: Institute of Sport, Exercise and Active Living (ISEAL), College of Sport and Exercise Science, Victoria University, Melbourne, Australia.
authors.forename: Fiona
authors.initials: F
authors.lastname: Munson
authors.affiliation: PathWest QEII Medical Centre, Perth, Australia.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Byrnes
authors.affiliation: Department of Physiology, Bosch Institute for Medical Research, University of Sydney, Sydney, Australia.
authors.forename: Daniele
authors.initials: D
authors.lastname: Vicari
authors.affiliation: Department of Physiology, Bosch Institute for Medical Research, University of Sydney, Sydney, Australia.
authors.forename: Tara C
authors.initials: TC
authors.lastname: Brennan-Speranza
authors.affiliation: Institute of Sport, Exercise and Active Living (ISEAL), College of Sport and Exercise Science, Victoria University, Melbourne, Australia; Murdoch Childrens Research Institute, Melbourne, Australia. Electronic address: Nir.Eynon@vu.edu.au.
authors.forename: Nir
authors.initials: N
authors.lastname: Eynon
mesh_terms: D000185:Actinin / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D016723:Bone Remodeling / Q000502:physiology*; D024042:Collagen Type I; D015444:Exercise / Q000502:physiology*; D005838:Genotype; D006801:Humans; D008297:Male; D015675:Osteocalcin; D010446:Peptide Fragments; D010455:Peptides; D011110:Polymorphism, Genetic; D011347:Procollagen; D055815:Young Adult
chemical_list: C118456:ACTN3 protein, human; D015415:Biomarkers; D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D015675:Osteocalcin; D000185:Actinin
keywords: ACTN3; Bone remodelling markers; Exercise; Gene variant