title: Loss of β-catenin induces multifocal periosteal chondroma-like masses in mice.
abstract: Osteochondromas and enchondromas are the most common tumors affecting the skeleton. Osteochondromas can occur as multiple lesions, such as those in patients with hereditary multiple exostoses. Unexpectedly, while studying the role of β-catenin in cartilage development, we found that its conditional deletion induces ectopic chondroma-like cartilage formation in mice. Postnatal ablation of β-catenin in cartilage induced lateral outgrowth of the growth plate within 2 weeks after ablation. The chondroma-like masses were present in the flanking periosteum by 5 weeks and persisted for more than 6 months after β-catenin ablation. These long-lasting ectopic masses rarely contained apoptotic cells. In good correlation, transplants of β-catenin-deficient chondrocytes into athymic mice persisted for a longer period of time and resisted replacement by bone compared to control wild-type chondrocytes. In contrast, a β-catenin signaling stimulator increased cell death in control chondrocytes. Immunohistochemical analysis revealed that the amount of detectable β-catenin in cartilage cells of osteochondromas obtained from hereditary multiple exostoses patients was much lower than that in hypertrophic chondrocytes in normal human growth plates. The findings in our study indicate that loss of β-catenin expression in chondrocytes induces periosteal chondroma-like masses and may be linked to, and cause, the persistence of cartilage caps in osteochondromas.
authors.affiliation: Translational Research Program in Pediatric Orthopaedics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Cantley
authors.forename: Cheri
authors.initials: C
authors.lastname: Saunders
authors.forename: Marta
authors.initials: M
authors.lastname: Guttenberg
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Candela
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ohta
authors.forename: Rika
authors.initials: R
authors.lastname: Yasuhara
authors.forename: Naoki
authors.initials: N
authors.lastname: Kondo
authors.forename: Federica
authors.initials: F
authors.lastname: Sgariglia
authors.forename: Shuji
authors.initials: S
authors.lastname: Asai
authors.forename: Xianrong
authors.initials: X
authors.lastname: Zhang
authors.forename: Ling
authors.initials: L
authors.lastname: Qin
authors.forename: Jacqueline T
authors.initials: JT
authors.lastname: Hecht
authors.forename: Di
authors.initials: D
authors.lastname: Chen
authors.forename: Masato
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Satoru
authors.initials: S
authors.lastname: Toyosawa
authors.forename: John P
authors.initials: JP
authors.lastname: Dormans
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Esko
authors.forename: Yu
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Iwamoto
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pacifici
authors.forename: Motomi
authors.initials: M
authors.lastname: Enomoto-Iwamoto
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D002356:Cartilage / Q000000981:diagnostic imaging / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D002812:Chondroma / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D002828:Choristoma / Q000000981:diagnostic imaging / Q000473:pathology; D024043:Collagen Type II / Q000378:metabolism; D006132:Growth Plate / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020287:In Situ Nick-End Labeling; D007211:Indoles / Q000494:pharmacology; D019426:Integrases / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D015831:Osteochondroma / Q000378:metabolism / Q000473:pathology; D010091:Oximes / Q000494:pharmacology; D010521:Periosteum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011859:Radiography; D012272:Ribs / Q000473:pathology; D013629:Tamoxifen / Q000494:pharmacology; D000071681:Tartrate-Resistant Acid Phosphatase; D051176:beta Catenin / Q000172:deficiency* / Q000378:metabolism
chemical_list: C483321:6-bromoindirubin-3'-oxime; D024043:Collagen Type II; D007211:Indoles; D007527:Isoenzymes; D010091:Oximes; D018809:Proliferating Cell Nuclear Antigen; D051176:beta Catenin; D013629:Tamoxifen; C045073:Cre recombinase; D019426:Integrases; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase