title: Evidence for Altered Canonical Wnt Signaling in the Trabecular Bone of Elderly Postmenopausal Women with Fragility Femoral Fracture.
abstract: Wnt signaling, a major regulator of bone formation and homeostasis, might be involved in the bone loss of osteoporotic patients and the consequent impaired response to fracture. Therefore we analyzed Wnt-related, osteogenic, and adipogenic genes in bone tissue of elderly postmenopausal women undergoing hip replacement for either femoral fracture or osteoarthritis. Bone specimens derived from the intertrochanteric region of the femurs of 25 women with fracture (F) and 29 with osteoarthritis without fracture (OA) were analyzed. Specific miRNAs were analyzed in bone and in matched blood samples. RUNX2, BGP, and OPG showed lower expression in F than in OA samples, while OSX, OPN, BSP, and RANKL were not different. Inhibitory genes of Wnt pathway were lower in F versus OA.β-Catenin protein levels were higher in F versus OA, whereas its cotranscriptional regulator (Lef1) was lower in F group. miR-204, which targets RUNX2, and miR-130a, which inhibits PPARγ, were lower and higher, respectively, in F versus OA serum samples. The present study showed an inefficient Wnt signal transduction in F group despite higherβ-catenin protein levels, consistent with the expected overall postfracture systemic activation towards osteogenesis. This transcriptional inefficiency could contribute to the osteoporotic bone fragility.
authors.affiliation: Bone Metabolism Unit, IRCCS Scientific Institute San Raffaele, Via Olgettina 60, 20132 Milano, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Bolamperti
authors.affiliation: Bone Metabolism Unit, IRCCS Scientific Institute San Raffaele, Via Olgettina 60, 20132 Milano, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Villa
authors.affiliation: Bone Metabolism Unit, IRCCS Scientific Institute San Raffaele, Via Olgettina 60, 20132 Milano, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Spinello
authors.affiliation: Orthopaedic Unit, IRCCS Scientific Institute San Raffaele, Via Olgettina 60, 20132 Milano, Italy.
authors.forename: Greta
authors.initials: G
authors.lastname: Manfredini
authors.affiliation: Bone Metabolism Unit, IRCCS Scientific Institute San Raffaele, Via Olgettina 60, 20132 Milano, Italy.
authors.forename: Emanuela
authors.identifier: 0000-0003-3087-2822
authors.initials: E
authors.lastname: Mrak
authors.affiliation: Orthopaedic Unit, IRCCS Scientific Institute San Raffaele, Via Olgettina 60, 20132 Milano, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Mezzadri
authors.affiliation: Orthopaedic Unit, IRCCS Scientific Institute San Raffaele, Via Olgettina 60, 20132 Milano, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Ometti
authors.affiliation: Orthopaedic Unit, IRCCS Scientific Institute San Raffaele, Via Olgettina 60, 20132 Milano, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Fraschini
authors.affiliation: Bone Metabolism Unit, IRCCS Scientific Institute San Raffaele, Via Olgettina 60, 20132 Milano, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Guidobono
authors.affiliation: Bone Metabolism Unit, IRCCS Scientific Institute San Raffaele, Via Olgettina 60, 20132 Milano, Italy.
authors.forename: Alessandro
authors.identifier: 0000-0003-1736-0531
authors.initials: A
authors.lastname: Rubinacci
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050659:Core Binding Factor Alpha 1 Subunit / Q000097:blood; D005260:Female; D005264:Femoral Fractures / Q000097:blood* / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000097:blood; D010003:Osteoarthritis / Q000097:blood / Q000473:pathology; D053244:Osteoprotegerin / Q000097:blood; D017698:Postmenopause / Q000097:blood*; D053245:RANK Ligand / Q000097:blood; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000097:blood
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C554019:MIRN130 microRNA, human; D035683:MicroRNAs; D053244:Osteoprotegerin; D053245:RANK Ligand; C493709:RUNX2 protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D051176:beta Catenin