title: F-spondin deficient mice have a high bone mass phenotype.
abstract: F-spondin is a pericellular matrix protein upregulated in developing growth plate cartilage and articular cartilage during osteoarthritis. To address its function in bone and cartilage in vivo, we generated mice that were deficient for the F-spondin gene, Spon1. Spon1-/- mice were viable and developed normally to adulthood with no major skeletal abnormalities. At 6 months, femurs and tibiae of Spon1-/- mice exhibited increased bone mass, evidenced by histological staining and micro CT analyses, which persisted up to 12 months. In contrast, no major abnormalities were observed in articular cartilage at any age group. Immunohistochemical staining of femurs and tibiae revealed increased levels of periostin, alkaline phosphate and tartrate resistant acid phosphatase (TRAP) activity in the growth plate region of Spon1-/- mice, suggesting elevated bone synthesis and turnover. However, there were no differences in serum levels of TRAP, the bone resorption marker, CTX-1, or osteoclast differentiation potential between genotypes. Knockout mice also exhibited reduced levels of TGF-β1 in serum and cultured costal chondrocytes relative to wild type. This was accompanied by increased levels of the BMP-regulatory SMADs, P-SMAD1/5 in tibiae and chondrocytes. Our findings indicate a previously unrecognized role for Spon1 as a negative regulator of bone mass. We speculate that Spon1 deletion leads to a local and systemic reduction of TGF-β levels resulting in increased BMP signaling and increased bone deposition in adult mice.
authors.affiliation: Division of Rheumatology, New York University School of Medicine and NYU Hospital for Joint Diseases, New York, New York, United States of America.
authors.forename: Glyn D
authors.initials: GD
authors.lastname: Palmer
authors.affiliation: Division of Rheumatology, New York University School of Medicine and NYU Hospital for Joint Diseases, New York, New York, United States of America.
authors.forename: Mukundan G
authors.initials: MG
authors.lastname: Attur
authors.affiliation: Division of Rheumatology, New York University School of Medicine and NYU Hospital for Joint Diseases, New York, New York, United States of America.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Division of Rheumatology, New York University School of Medicine and NYU Hospital for Joint Diseases, New York, New York, United States of America.
authors.forename: James
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada.
authors.forename: Paxton
authors.initials: P
authors.lastname: Moon
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada.
authors.forename: Frank
authors.initials: F
authors.lastname: Beier
authors.affiliation: Division of Rheumatology, New York University School of Medicine and NYU Hospital for Joint Diseases, New York, New York, United States of America.
authors.forename: Steven B
authors.initials: SB
authors.lastname: Abramson
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001842:Bone and Bones / Q000033:anatomy & histology* / Q000166:cytology / Q000000981:diagnostic imaging / Q000378:metabolism*; D019902:Chondrocytes / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000172:deficiency*; D023061:Gene Order; D018390:Gene Targeting; D005838:Genotype; D051379:Mice; D018345:Mice, Knockout; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D010766:Phosphorylation; D051785:Smad Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D055114:X-Ray Microtomography
chemical_list: D015415:Biomarkers; D016326:Extracellular Matrix Proteins; C552523:F-spondin protein, mouse; D051785:Smad Proteins; D016212:Transforming Growth Factor beta