title: Estrogen inhibits Dlk1/FA1 production: a potential mechanism for estrogen effects on bone turnover.
abstract: We have recently identified delta-like 1/fetal antigen 1 (Dlk1/FA1) as a novel regulator of bone mass that functions to mediate bone loss under estrogen deficiency in mice. In this report, we investigated the effects of estrogen (E) deficiency and E replacement on serum (s) levels of Dlk1/FA1 (s-Dlk1FA1) and its correlation with bone turnover markers. s-Dlk1/FA1 and bone turnover markers (serum cross-linked C-telopeptide [s-CTX] and serum osteocalcin) were measured in two cohorts: a group of pre- and postmenopausal women (n = 100) and a group of postmenopausal women, where half had received estrogen-replacement therapy (ERT, n = 166). s-Dlk1/FA1 and s-CTX were elevated in postmenopausal E-deficient women compared with premenopausal E-replete women (both p < 0.001). s-Dlk1/FA1 was correlated with s-CTX (r = 0.30, p < 0.01). ERT in postmenopausal women decreased s-Dlk1/FA1, as well as s-CTX and s-osteoclacin (all p < .0001). Changes in s-Dlk1 were significantly correlated with those observed in s-CTX (r = 0.18, p < 0.05) and s-osteocalcin (r = 0.28, p < 0.001). In conclusion, s-Dlk1/FA1 is influenced by E-deficiency and is correlated with bone turnover. Increased levels of s-Dlk1/FA1 in postmenopausal women may be a mechanism mediating the effects of estrogen deficiency on bone turnover.
authors.affiliation: Endocrine Research Laboratory (KMEB), Department of Endocrinology and Metabolism, Odense University Hospital and University of Southern Denmark, Odense, Denmark. babdallah@health.sdu.dk
authors.forename: Basem M
authors.initials: BM
authors.lastname: Abdallah
authors.forename: Anne-Christine
authors.initials: AC
authors.lastname: Bay-Jensen
authors.forename: Bhuma
authors.initials: B
authors.lastname: Srinivasan
authors.forename: Nadine C
authors.initials: NC
authors.lastname: Tabassi
authors.forename: Patrick
authors.initials: P
authors.lastname: Garnero
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Delaissé
authors.forename: Sundeep
authors.initials: S
authors.lastname: Khosla
authors.forename: Moustapha
authors.initials: M
authors.lastname: Kassem
mesh_terms: D016723:Bone Remodeling; D002135:Calcium-Binding Proteins; D015331:Cohort Studies; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000502:physiology*; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008875:Middle Aged
chemical_list: D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; D004967:Estrogens; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins