title: Functions of Rho family of small GTPases and Rho-associated coiled-coil kinases in bone cells during differentiation and mineralization.
abstract: Members of Rho-associated coiled-coil kinases (ROCKs) are effectors of Rho family of small GTPases. ROCKs have multiple functions that include regulation of cellular contraction and polarity, adhesion, motility, proliferation, apoptosis, differentiation, maturation and remodeling of the extracellular matrix (ECM).
  
  
  
  Here, we focus on the action of RhoA and RhoA effectors, ROCK1 and ROCK2, in cells related to tissue mineralization: mesenchymal stem cells, chondrocytes, preosteoblasts, osteoblasts, osteocytes, lining cells and osteoclasts.
  
  
  
  The activation of the RhoA/ROCK pathway promotes stress fiber formation and reduces chondrocyte and osteogenic differentiations, in contrast to that in mesenchymal stem cells which stimulated the osteogenic and the chondrogenic differentiation. The effects of Rac1 and Cdc42 in promoting chondrocyte hypertrophy and of Rac1, Rac2 and Cdc42 in osteoclast are discussed. In addition, members of the Rho family of GTPases such Rac1, Rac2, Rac3 and Cdc42, acting upstream of ROCK and/or other protein effectors, may compensate the actions of RhoA, affecting directly or indirectly the actions of ROCKs as well as other protein effectors.
  
  
  
  ROCK activity can trigger cartilage degradation and affect bone formation, therefore these kinases may represent a possible therapeutic target to treat osteoarthritis and osseous diseases. Inhibition of Rho/ROCK activity in chondrocytes prevents cartilage degradation, stimulate mineralization of osteoblasts and facilitate bone formation around implanted metals. Treatment with osteoprotegerin results in a significant decrease in the expression of Rho GTPases, ROCK1 and ROCK2, reducing bone resorption. Inhibition of ROCK signaling increases osteoblast differentiation in a topography-dependent manner.
authors.affiliation: Department of Biochemistry, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteura Str., 02-093 Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Strzelecka-Kiliszek
authors.affiliation: ICBMS, UMR CNRS 5246, University of Lyon 1, Bâtiment Raulin, 43 Bd du 11 novembre 1918, 69622 Villeurbanne Cedex, France; Université de Lyon, 69622 Villeurbanne Cedex, France; Université Lyon 1, 69622 Villeurbanne Cedex, France; INSA de Lyon, 69621 Villeurbanne Cedex, France; CPE Lyon, 69616 Villeurbanne Cedex, France; ICBMS CNRS UMR 5246, 69622 Villeurbanne Cedex, France.
authors.forename: Saida
authors.initials: S
authors.lastname: Mebarek
authors.affiliation: Department of Biochemistry, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteura Str., 02-093 Warsaw, Poland; ICBMS, UMR CNRS 5246, University of Lyon 1, Bâtiment Raulin, 43 Bd du 11 novembre 1918, 69622 Villeurbanne Cedex, France; Université de Lyon, 69622 Villeurbanne Cedex, France.
authors.forename: Monika
authors.initials: M
authors.lastname: Roszkowska
authors.affiliation: ICBMS, UMR CNRS 5246, University of Lyon 1, Bâtiment Raulin, 43 Bd du 11 novembre 1918, 69622 Villeurbanne Cedex, France; Université de Lyon, 69622 Villeurbanne Cedex, France; Université Lyon 1, 69622 Villeurbanne Cedex, France; INSA de Lyon, 69621 Villeurbanne Cedex, France; CPE Lyon, 69616 Villeurbanne Cedex, France; ICBMS CNRS UMR 5246, 69622 Villeurbanne Cedex, France.
authors.forename: René
authors.initials: R
authors.lastname: Buchet
authors.affiliation: ICBMS, UMR CNRS 5246, University of Lyon 1, Bâtiment Raulin, 43 Bd du 11 novembre 1918, 69622 Villeurbanne Cedex, France; Université de Lyon, 69622 Villeurbanne Cedex, France; Université Lyon 1, 69622 Villeurbanne Cedex, France; INSA de Lyon, 69621 Villeurbanne Cedex, France; CPE Lyon, 69616 Villeurbanne Cedex, France; ICBMS CNRS UMR 5246, 69622 Villeurbanne Cedex, France.
authors.forename: David
authors.initials: D
authors.lastname: Magne
authors.affiliation: Department of Biochemistry, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteura Str., 02-093 Warsaw, Poland. Electronic address: s.pikula@nencki.gov.pl.
authors.forename: Slawomir
authors.initials: S
authors.lastname: Pikula
mesh_terms: D000818:Animals; D002113:Calcification, Physiologic / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D006801:Humans; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D054460:rho-Associated Kinases; D020559:Monomeric GTP-Binding Proteins; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein
keywords: Bone cells; Differentiation; Mineralization; ROCK; Signal transduction; Vesicles