Dual functional roles of dentin matrix protein 1. Implications in biomineralization and gene transcription by activation of intracellular Ca2+ store.
Dentin matrix protein 1 (DMP1) is a bone- and teeth-specific protein initially identified from mineralized dentin. Here we report that DMP1 is primarily localized in the nuclear compartment of undifferentiated osteoblasts. In the nucleus, DMP1 acts as a transcriptional component for activation of osteoblast-specific genes like osteocalcin. During the early phase of osteoblast maturation, Ca(2+) surges into the nucleus from the cytoplasm, triggering the phosphorylation of DMP1 by a nuclear isoform of casein kinase II. This phosphorylated DMP1 is then exported out into the extracellular matrix, where it regulates nucleation of hydroxyapatite. Thus, DMP1 is a unique molecule that initiates osteoblast differentiation by transcription in the nucleus and orchestrates mineralized matrix formation extracellularly, at later stages of osteoblast maturation. The data presented here represent a paradigm shift in the understanding of DMP1 function. This information is crucial in understanding normal bone formation, remodeling, fracture healing, and skeletal tissue repair.
Narayanan
Karthikeyan
K
Department of Oral Biology, University of Illinois, Chicago, Illinois 60612, USA.
Ramachandran
Amsaveni
A
Hao
Jianjun
J
He
Gen
G
Park
Kyle Won
KW
Cho
Michael
M
George
Anne
A
D000818:Animals; D002113:Calcification, Physiologic / Q000502:physiology; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics; D002467:Cell Nucleus / Q000502:physiology; D016326:Extracellular Matrix Proteins; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology; D010750:Phosphoproteins / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology
C513308:Dmp1 protein, mouse; D016326:Extracellular Matrix Proteins; D010750:Phosphoproteins; D002118:Calcium