Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism. Academic Article uri icon


  • 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 (P(i)) 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.

published proceedings

  • Nat Genet

altmetric score

  • 33

author list (cited authors)

  • Feng, J. Q., Ward, L. M., Liu, S., Lu, Y., Xie, Y., Yuan, B., ... White, K. E.

citation count

  • 979

complete list of authors

  • Feng, Jian Q||Ward, Leanne M||Liu, Shiguang||Lu, Yongbo||Xie, Yixia||Yuan, Baozhi||Yu, Xijie||Rauch, Frank||Davis, Siobhan I||Zhang, Shubin||Rios, Hector||Drezner, Marc K||Quarles, L Darryl||Bonewald, Lynda F||White, Kenneth E

publication date

  • January 2006