title: Altered bone development and turnover in transgenic mice over-expressing lipocalin-2 in bone.
abstract: Lipocalin-2 (LCN2) is a protein largely expressed in many tissues, associated with different biological phenomena such as cellular differentiation, inflammation and cancer acting as a survival/apoptotic signal. We found that LCN2 was expressed during osteoblast differentiation and we generated transgenic (Tg) mice over-expressing LCN2 in bone. Tg mice were smaller and presented bone microarchitectural changes in both endochondral and intramembranous bones. In particular, Tg bones displayed a thinner layer of cortical bone and a decreased trabecular number. Osteoblast bone matrix deposition was reduced and osteoblast differentiation was slowed-down. Differences were also observed in the growth plate of young transgenic mice where chondrocyte displayed a more immature phenotype and a lower proliferation rate. In bone marrow cell cultures from transgenic mice, the number of osteoclast progenitors was increased whereas in vivo it was increased the number of mature osteoclasts expressing tartrate-resistant acid phosphatase (TRAP). Finally, while osteoprotegerin (OPG) levels remained unchanged, the expression of the conventional receptor activator of nuclear factor-κB ligand (RANKL) and of the IL-6 was enhanced in Tg mice. In conclusion, we found that LCN2 plays a role in bone development and turnover having both a negative effect on bone formation, by affecting growth plate development and interfering with osteoblast differentiation, and a positive effect on bone resorption by enhancing osteoclast compartment.
authors.affiliation: Dipartimento di Medicina Sperimentale, Universita' di Genova & IRCCS AOU San Martino-IST, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: Delfina
authors.initials: D
authors.lastname: Costa
authors.forename: Edoardo
authors.initials: E
authors.lastname: Lazzarini
authors.forename: Barbara
authors.initials: B
authors.lastname: Canciani
authors.forename: Alessandra
authors.initials: A
authors.lastname: Giuliani
authors.forename: Raffaele
authors.initials: R
authors.lastname: Spanò
authors.forename: Katia
authors.initials: K
authors.lastname: Marozzi
authors.forename: Adrian
authors.initials: A
authors.lastname: Manescu
authors.forename: Ranieri
authors.initials: R
authors.lastname: Cancedda
authors.forename: Sara
authors.initials: S
authors.lastname: Tavella
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000209:Acute-Phase Proteins / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D049628:Body Size; D001846:Bone Development; D016723:Bone Remodeling; D001862:Bone Resorption / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D005269:Femur / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D006132:Growth Plate / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D015850:Interleukin-6 / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D015513:Oncogene Proteins / Q000378:metabolism*; D009929:Organ Size; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D011859:Radiography; D011956:Receptors, Cell Surface / Q000378:metabolism; D015203:Reproducibility of Results; D000071681:Tartrate-Resistant Acid Phosphatase; D019076:Transgenes / Q000235:genetics
chemical_list: D000209:Acute-Phase Proteins; D015850:Interleukin-6; D007527:Isoenzymes; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D011956:Receptors, Cell Surface; C071332:Lcn2 protein, mouse; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase