Ontology highlight
ABSTRACT:
SUBMITTER: Florio M
PROVIDER: S-EPMC4894982 | biostudies-literature | 2016 May
REPOSITORIES: biostudies-literature
Florio Monica M Gunasekaran Kannan K Stolina Marina M Li Xiaodong X Liu Ling L Tipton Barbara B Salimi-Moosavi Hossein H Asuncion Franklin J FJ Li Chaoyang C Sun Banghua B Tan Hong Lin HL Zhang Li L Han Chun-Ya CY Case Ryan R Duguay Amy N AN Grisanti Mario M Stevens Jennitte J Pretorius James K JK Pacheco Efrain E Jones Heidi H Chen Qing Q Soriano Brian D BD Wen Jie J Heron Brenda B Jacobsen Frederick W FW Brisan Emil E Richards William G WG Ke Hua Zhu HZ Ominsky Michael S MS
Nature communications 20160527
Inhibition of the Wnt antagonist sclerostin increases bone mass in patients with osteoporosis and in preclinical animal models. Here we show increased levels of the Wnt antagonist Dickkopf-1 (DKK-1) in animals treated with sclerostin antibody, suggesting a negative feedback mechanism that limits Wnt-driven bone formation. To test our hypothesis that co-inhibition of both factors further increases bone mass, we engineer a first-in-class bispecific antibody with single residue pair mutations in th ...[more]