We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism.
- Authors
Feng, Jian Q.; Ward, Leanne M.; Shiguang Liu; Yongbo Lu; Yixia Xie; Baozhi Yuan; Xijie Yu; Rauch, Frank; Davis, Siobhan I.; Shubin Zhang; Rios, Hector; Drezner, Marc K.; Quarles, L. Darryl; Bonewald, Lynda F.; White, Kenneth E.
- Abstract
The osteocyte, a terminally differentiated cell comprising 90%–95% of all bone cells, may have multiple functions, including acting as a mechanosensor in bone (re)modeling. Dentin matrix protein 1 (encoded by DMP1) is highly expressed in osteocytes and, when deleted in mice, results in a hypomineralized bone phenotype. We investigated the potential for this gene not only to direct skeletal mineralization but also to regulate phosphate (Pi) homeostasis. Both Dmp1-null mice and individuals with a newly identified disorder, autosomal recessive hypophosphatemic rickets, manifest rickets and osteomalacia with isolated renal phosphate-wasting associated with elevated fibroblast growth factor 23 (FGF23) levels and normocalciuria. Mutational analyses showed that autosomal recessive hypophosphatemic rickets family carried a mutation affecting the DMP1 start codon, and a second family carried a 7-bp deletion disrupting the highly conserved DMP1 C terminus. Mechanistic studies using Dmp1-null mice demonstrated that absence of DMP1 results in defective osteocyte maturation and increased FGF23 expression, leading to pathological changes in bone mineralization. Our findings suggest a bone-renal axis that is central to guiding proper mineral metabolism.
- Subjects
DENTIN; EXTRACELLULAR matrix proteins; PROTEINS; RICKETS; OSTEOMALACIA; BONE diseases; MINERAL metabolism; HUMAN genetics
- Publication
Nature Genetics, 2006, Vol 38, Issue 11, p1310
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng1905