TY  - JOUR
A1  - Lotinun, Sutada
A1  - Kiviranta, Riku
A1  - Matsubara, Takuma
A1  - Alzate, Jorge A.
A1  - Neff, Lynn
A1  - Lüth, Anja
A1  - Koskivirta, Ilpo
A1  - Kleuser, Burkhard
A1  - Vacher, Jean
A1  - Vuorio, Eero
A1  - Horne, William C.
A1  - Baron, Roland
T1  - Osteoclast-specific cathepsin K deletion stimulates S1P-dependent bone formation
JF  - The journal of clinical investigation
N2  - Cathepsin K (CTSK) is secreted by osteoclasts to degrade collagen and other matrix proteins during bone resorption. Global deletion of Ctsk in mice decreases bone resorption, leading to osteopetrosis, but also increases the bone formation rate (BFR). To understand how Ctsk deletion increases the BFR, we generated osteoclast- and osteoblast-targeted Ctsk knockout mice using floxed Ctsk alleles. Targeted ablation of Ctsk in hematopoietic cells, or specifically in osteoclasts and cells of the monocyte-osteoclast lineage, resulted in increased bone volume and BFR as well as osteoclast and osteoblast numbers. In contrast, targeted deletion of Ctsk in osteoblasts had no effect on bone resorption or BFR, demonstrating that the increased BFR is osteoclast dependent. Deletion of Ctsk in osteoclasts increased their sphingosine kinase 1 (Sphk1) expression. Conditioned media from Ctsk-deficient osteoclasts, which contained elevated levels of sphingosine-l-phosphate (S1P), increased alkaline phosphatase and mineralized nodules in osteoblast cultures. An S1P(1,3) receptor antagonist inhibited these responses. Osteoblasts derived from mice with Ctsk-deficient osteoclasts had an increased RANKL/OPG ratio, providing a positive feedback loop that increased the number of osteoclasts. Our data provide genetic evidence that deletion of CTSK in osteoclasts enhances bone formation in vivo by increasing the generation of osteoclast-derived S1P.
Y1  - 2013
U6  - https://doi.org/10.1172/JCI64840
SN  - 0021-9738
VL  - 123
IS  - 2
SP  - 666
EP  - 681
PB  - American Society for Clinical Investigation
CY  - Ann Arbor
ER  - 
TY  - JOUR
A1  - Weiss, Jonathan R.
A1  - Qiu, Qiang
A1  - Barbot, Sylvain
A1  - Wright, Tim J.
A1  - Foster, James H.
A1  - Saunders, Alexander
A1  - Brooks, Benjamin A.
A1  - Bevis, Michael
A1  - Kendrick, Eric
A1  - Ericksen, Todd L.
A1  - Avery, Jonathan
A1  - Smalley, Robert
A1  - Cimbaro, Sergio R.
A1  - Lenzano, Luis Eduardo
A1  - Baron, Jorge
A1  - Carlos Baez, Juan
A1  - Echalar, Arturo
T1  - Illuminating subduction zone rheological properties in the wake of a giant earthquake
JF  - Science Advances
N2  - Deformation associated with plate convergence at subduction zones is accommodated by a complex system involving fault slip and viscoelastic flow. These processes have proven difficult to disentangle. The 2010 M-w 8.8 Maule earthquake occurred close to the Chilean coast within a dense network of continuously recording Global Positioning System stations, which provide a comprehensive history of surface strain. We use these data to assemble a detailed picture of a structurally controlled megathrust fault frictional patchwork and the three-dimensional rheological and time-dependent viscosity structure of the lower crust and upper mantle, all of which control the relative importance of afterslip and viscoelastic relaxation during postseismic deformation. These results enhance our understanding of subduction dynamics including the interplay of localized and distributed deformation during the subduction zone earthquake cycle.
Y1  - 2019
U6  - https://doi.org/10.1126/sciadv.aax6720
SN  - 2375-2548
VL  - 5
IS  - 12
PB  - American Assoc. for the Advancement of Science
CY  - Washington
ER  -