PMID- 10350213
OWN - NLM
STAT- MEDLINE
DCOM- 19990803
LR  - 20071115
IS  - 0171-9335 (Print)
IS  - 0171-9335 (Linking)
VI  - 78
IP  - 4
DP  - 1999 Apr
TI  - Rac-GTPase, osteoclast cytoskeleton and bone resorption.
PG  - 249-55
AB  - The members of the Rho-GTPase subfamily, Rac1 and Rac2, are intimately involved
      in the organization of the cytoskeleton, and the p21-activated kinases or PAKs
      are targets of these proteins. Rac1 and Rac2 are also essential components of
      NADPH oxidase, the enzyme responsible for generating free radicals. The
      cytoskeleton modulates the adhesion of osteoclasts to bone and its subsequent
      resorption. These cells contain NADPH diaphorase activity, and free radicals
      influence bone resorption. The influence of Rac1, Rac2 and PAK1 on the
      cytoskeleton, resorbing activity and NADPH diaphorase activity of disaggregated
      rat osteoclasts was investigated by permeabilisation with saponin and introducing
      specific anti-Rac1, anti-Rac2 or anti-PAK1 antibodies. Rhodamine-phalloidin stain
      was used to identify actin in osteoclasts cultured on plastic slides, and the
      bone-slice method was used to measure resorption. Saponin permeabilisation did
      not affect the cytoskeletal organization or bone resorption. Anti-Rac antibodies 
      caused dose- and time-dependent cytoskeletal changes. The osteoclasts rounded up 
      and developed retraction fibers; actin rings were disrupted and large actin dots 
      were seen at the periphery of the cells. Osteoclast resorptive activity was
      depressed after incubation with the antibodies. The total area resorbed by
      treated cells and the mean pit area were smaller than those of controls.
      Anti-PAK1 antibody caused similar changes. None of the antibodies altered the
      NADPH diaphorase activity. Thus, Rac-GTPases are present in rat osteoclasts and
      are involved in the organization of the actin cytoskeleton and in resorptive
      activity. These effects may be mediated by PAK1 kinase, but do not influence
      osteoclast NADPH diaphorase activity.
FAU - Razzouk, S
AU  - Razzouk S
AD  - CNRS-UPR 1524, INRA-LNSA-Bat 221, Jouy en Josas/France.
FAU - Lieberherr, M
AU  - Lieberherr M
FAU - Cournot, G
AU  - Cournot G
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Eur J Cell Biol
JT  - European journal of cell biology
JID - 7906240
RN  - 0 (Actins)
RN  - 0 (GTPase-Activating Proteins)
RN  - 0 (Proteins)
RN  - 53-59-8 (NADP)
RN  - EC 1.8.1.4 (Dihydrolipoamide Dehydrogenase)
RN  - EC 2.7.11.1 (Pak1 protein, rat)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (p21-Activated Kinases)
SB  - IM
MH  - Actins/metabolism
MH  - Animals
MH  - Bone Resorption/*metabolism
MH  - Cytoskeleton/*metabolism
MH  - Dihydrolipoamide Dehydrogenase/metabolism
MH  - Dose-Response Relationship, Drug
MH  - GTPase-Activating Proteins
MH  - NADP/metabolism
MH  - Osteoclasts/*metabolism
MH  - Protein-Serine-Threonine Kinases/analysis
MH  - Proteins/analysis/*metabolism
MH  - Rats
MH  - Signal Transduction
MH  - Time Factors
MH  - p21-Activated Kinases
EDAT- 1999/06/01 00:00
MHDA- 1999/06/01 00:01
CRDT- 1999/06/01 00:00
PHST- 1999/06/01 00:00 [pubmed]
PHST- 1999/06/01 00:01 [medline]
PHST- 1999/06/01 00:00 [entrez]
AID - S0171-9335(99)80058-2 [pii]
AID - 10.1016/S0171-9335(99)80058-2 [doi]
PST - ppublish
SO  - Eur J Cell Biol. 1999 Apr;78(4):249-55. doi: 10.1016/S0171-9335(99)80058-2.