PMID- 11038178
OWN - NLM
STAT- MEDLINE
DCOM- 20001120
LR  - 20230509
IS  - 0021-9525 (Print)
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Linking)
VI  - 151
IP  - 2
DP  - 2000 Oct 16
TI  - Decreased c-Src expression enhances osteoblast differentiation and bone 
      formation.
PG  - 311-20
AB  - c-src deletion in mice leads to osteopetrosis as a result of reduced bone 
      resorption due to an alteration of the osteoclast. We report that 
      deletion/reduction of Src expression enhances osteoblast differentiation and bone 
      formation, contributing to the increase in bone mass. Bone histomorphometry 
      showed that bone formation was increased in Src null compared with wild-type 
      mice. In vitro, alkaline phosphatase (ALP) activity and nodule mineralization 
      were increased in primary calvarial cells and in SV40-immortalized osteoblasts 
      from Src(-/-) relative to Src(+/+) mice. Src-antisense oligodeoxynucleotides 
      (AS-src) reduced Src levels by approximately 60% and caused a similar increase in 
      ALP activity and nodule mineralization in primary osteoblasts in vitro. Reduction 
      in cell proliferation was observed in primary and immortalized Src(-/-) 
      osteoblasts and in normal osteoblasts incubated with the AS-src. Semiquantitative 
      reverse transcriptase-PCR revealed upregulation of ALP, Osf2/Cbfa1 transcription 
      factor, PTH/PTHrP receptor, osteocalcin, and pro-alpha 2(I) collagen in 
      Src-deficient osteoblasts. The expression of the bone matrix protein osteopontin 
      remained unchanged. Based on these results, we conclude that the reduction of Src 
      expression not only inhibits bone resorption, but also stimulates osteoblast 
      differentiation and bone formation, suggesting that the osteogenic cells may 
      contribute to the development of the osteopetrotic phenotype in Src-deficient 
      mice.
FAU - Marzia, M
AU  - Marzia M
AD  - Department of Histology and General Embryology, University La Sapienza, 00161 
      Rome, Italy.
FAU - Sims, N A
AU  - Sims NA
FAU - Voit, S
AU  - Voit S
FAU - Migliaccio, S
AU  - Migliaccio S
FAU - Taranta, A
AU  - Taranta A
FAU - Bernardini, S
AU  - Bernardini S
FAU - Faraggiana, T
AU  - Faraggiana T
FAU - Yoneda, T
AU  - Yoneda T
FAU - Mundy, G R
AU  - Mundy GR
FAU - Boyce, B F
AU  - Boyce BF
FAU - Baron, R
AU  - Baron R
FAU - Teti, A
AU  - Teti A
LA  - eng
GR  - E.0831/TI_/Telethon/Italy
GR  - R01 AR042927/AR/NIAMS NIH HHS/United States
GR  - AR42927/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Core Binding Factor Alpha 1 Subunit)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (Parathyroid Hormone)
RN  - 0 (Receptors, Parathyroid Hormone)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.10.2 (Proto-Oncogene Proteins pp60(c-src))
RN  - EC 3.1.3.1 (Alkaline Phosphatase)
SB  - IM
MH  - Alkaline Phosphatase/biosynthesis
MH  - Animals
MH  - Bone Resorption/genetics
MH  - Cell Differentiation
MH  - Cell Division
MH  - Cells, Cultured
MH  - Core Binding Factor Alpha 1 Subunit
MH  - Gene Expression Regulation/drug effects
MH  - Mice
MH  - Mice, Mutant Strains
MH  - *Neoplasm Proteins
MH  - Oligonucleotides, Antisense/pharmacology
MH  - Osteoblasts/*cytology
MH  - Osteogenesis/*genetics
MH  - Osteopetrosis/genetics
MH  - Parathyroid Hormone/biosynthesis
MH  - Phenotype
MH  - Proto-Oncogene Proteins pp60(c-src)/*genetics
MH  - Receptors, Parathyroid Hormone/biosynthesis
MH  - Skull/cytology
MH  - Transcription Factors/biosynthesis
MH  - Transcription, Genetic
PMC - PMC2192638
EDAT- 2000/10/19 11:00
MHDA- 2001/02/28 10:01
PMCR- 2001/04/16
CRDT- 2000/10/19 11:00
PHST- 2000/10/19 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/10/19 11:00 [entrez]
PHST- 2001/04/16 00:00 [pmc-release]
AID - 0002094 [pii]
AID - 10.1083/jcb.151.2.311 [doi]
PST - ppublish
SO  - J Cell Biol. 2000 Oct 16;151(2):311-20. doi: 10.1083/jcb.151.2.311.