ROCK1 ja ROCK2 signalointialueelta lähdetietoa, Kalsium ja mineralisoitumisen säätelyalue .

. 2017 May;1861(5 Pt A):1009-1023.

doi: 10.1016/j.bbagen.2017.02.005. Epub 2017 Feb 8. Functions of Rho family of small GTPases and Rho-associated coiled-coil kinases  (ROCKa) in bone cells during differentiation and mineralization

Agnieszka Strzelecka-Kiliszek  ¹ , Saida Mebarek  ² , Monika Roszkowska  ³ , René Buchet  ² , David Magne  ² , Slawomir Pikula  ⁴

Affiliations

• PMID: 28188861
• DOI: 10.1016/j.bbagen.2017.02.005

Abstract

Background: 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).

  Scope of the review:   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.

Major conclusions: 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.

General significance: 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.

Keywords: Bone cells; Differentiation; Mineralization; ROCK; Signal transduction; Vesicles.

 

 

 https://www.pnas.org/doi/10.1073/pnas.1721298115

Different roles of myocardial ROCK1 and ROCK2 in cardiac dysfunction and postcapillary pulmonary hypertension in mice

Shinichiro Sunamura, Kimio Satoh, Ryo Kurosawa, +13 , and Hiroaki Shimokawa shimo@cardio.med.tohoku.ac.jpAuthors Info & Affiliations

Edited by J. G. Seidman, Harvard Medical School, Boston, MA, and approved June 21, 2018 (received for review December 8, 2017)

July 9, 2018

115 (30) E7129-E7138

https://doi.org/10.1073/pnas.1721298115

 Significance

Our data suggest opposite roles for ROCK1 and ROCK2 in cardiomyocytes. Additional studies identified downstream targets of ROCK1 and ROCK2 related to calcium handling, mitochondrial function, and oxidative stress. In particular, our findings indicate that cyclophilin A (CyPA) and basigin (Bsg), both of which augment oxidative stress, enhanced cardiac dysfunction and postcapillary pulmonary hypertension (PH) in cROCK1^−/− mice, while their expressions were lower in cROCK2^−/− mice. Finally, screening of the public chemical library in the Drug Discovery Initiative enabled us to identify compounds that reduce the expressions of CyPA and Bsg. Among them, celastrol suppressed the expression of both CyPA and Bsg in heart and lungs, thereby ameliorating both heart failure and postcapillary PH in mice.

 

Basigin on CD147, ISBT024 veriryhmä OK joka on miltei joka ihmisellä) 

 https://pubmed.ncbi.nlm.nih.gov/?term=HIV-1%2C+Basigin%2C+cyclophilin&sort=date