title: Tendon protein synthesis rate in classic Ehlers-Danlos patients can be stimulated with insulin-like growth factor-I.
abstract: The classic form of Ehlers-Danlos syndrome (cEDS) is an inherited connective tissue disorder, where mutations in type V collagen-encoding genes result in abnormal collagen fibrils. Thus the cEDS patients have pathological connective tissue morphology and low stiffness, but the rate of connective tissue protein turnover is unknown. We investigated whether cEDS affected the protein synthesis rate in skin and tendon, and whether this could be stimulated in tendon tissue with insulin-like growth factor-I (IGF-I). Five patients with cEDS and 10 healthy, matched controls (CTRL) were included. One patellar tendon of each participant was injected with 0.1 ml IGF-I (Increlex, Ipsen, 10 mg/ml) and the contralateral tendon with 0.1 ml isotonic saline as control. The injections were performed at both 24 and 6 h prior to tissue sampling. The fractional synthesis rate (FSR) of proteins in skin and tendon was measured with the stable isotope technique using a flood-primed continuous infusion over 6 h. After the infusion one skin biopsy and two tendon biopsies (one from each patellar tendon) were obtained. We found similar baseline FSR values in skin and tendon in the cEDS patients and controls [skin: 0.005 ± 0.002 (cEDS) and 0.007 ± 0.002 (CTRL); tendon: 0.008 ± 0.001 (cEDS) and 0.009 ± 0.002 (CTRL) %/h, mean ± SE]. IGF-I injections significantly increased FSR values in cEDS patients but not in controls (delta values: cEDS 0.007 ± 0.002, CTRL 0.001 ± 0.001%/h). In conclusion, baseline protein synthesis rates in connective tissue appeared normal in cEDS patients, and the patients responded with an increased tendon protein synthesis rate to IGF-I injections.
authors.affiliation: Institute of Sports Medicine, Department of Orthopaedic Surgery, Bispebjerg Hospital, and Centre for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; rieharboenielsen@gmail.com.
authors.forename: Rie Harboe
authors.initials: RH
authors.lastname: Nielsen
authors.affiliation: Institute of Sports Medicine, Department of Orthopaedic Surgery, Bispebjerg Hospital, and Centre for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Institute of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; and.
authors.forename: Lars
authors.initials: L
authors.lastname: Holm
authors.affiliation: Institute of Sports Medicine, Department of Orthopaedic Surgery, Bispebjerg Hospital, and Centre for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Jacob Kildevang
authors.initials: JK
authors.lastname: Jensen
authors.affiliation: Institute of Sports Medicine, Department of Orthopaedic Surgery, Bispebjerg Hospital, and Centre for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Katja Maria
authors.initials: KM
authors.lastname: Heinemeier
authors.affiliation: Department of Infectious Medicine and Rheumatology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Remvig
authors.affiliation: Institute of Sports Medicine, Department of Orthopaedic Surgery, Bispebjerg Hospital, and Centre for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Michael
authors.initials: M
authors.lastname: Kjaer
mesh_terms: D000328:Adult; D000368:Aged; D004535:Ehlers-Danlos Syndrome / Q000378:metabolism*; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D014176:Protein Biosynthesis / Q000187:drug effects*; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D013710:Tendons / Q000187:drug effects* / Q000378:metabolism; D055815:Young Adult
chemical_list: D007334:Insulin-Like Growth Factor I
keywords: COL5A1; COL5A2; col5a1+/−; proline