Sclerostin antibody (Scl-Ab) improves osteomalacia phenotype in dentin matrix protein 1(Dmp1) knockout mice with little impact on serum levels of phosphorus and FGF23

Yinshi Ren, Xianglong Han, Yan Jing, Baozhi Yuan, Huazhu Ke, Min Liu, Jian Q. Feng

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Unlike treatments for most rickets, the treatment using 1,25-(OH)2 vitamin D3 has little efficacy on patients with hypophosphatemic rickets, a set of rare genetic diseases. Thus, understanding the local cause for osteomalacia in hypophosphatemic rickets and developing an effective treatment to restore mineralization in this rare disease has been a longstanding goal in medicine. Here, we used Dmp1 knockout (KO) mice (whose mutations led to the same type of autosomal recessive hypophosphatemic rickets in humans) as the model in which the monoclonal antibody of sclerostin (Scl-Ab) was tested in two age groups for 8 weeks: the prevention group (starting at age 4 weeks) and the treatment group (starting at age 12 weeks). Applications of Scl-Ab greatly improved the osteomalacia phenotype (> 15%) and the biomechanical properties (3-point bending, ~ 60%) in the treated long-bone group. Our studies not only showed improvement of the osteomalacia in the alveolar bone, which has the highest bone metabolism rate, as well as the long bone phenotypes in treated mice. All these improvements attributed to the use of Scl-Ab are independent of the change in serum levels of phosphorus and FGF23, since Scl-Ab had little efficacy on those parameters. Finally, we propose a model to explain how Scl-Ab can improve the Dmp1 KO osteomalacia phenotype, in which the sclerostin level is already low.

Original languageEnglish (US)
Pages (from-to)151-161
Number of pages11
JournalMatrix Biology
Volume52-54
DOIs
StatePublished - May 1 2016
Externally publishedYes

Keywords

  • DMP1
  • Hypophosphatemic rickets
  • Osteocytes
  • PDL
  • SOST
  • Sclerostin antibody

ASJC Scopus subject areas

  • Molecular Biology

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