Abstract
The serine protease thrombin stimulates proliferation in osteoblasts, but decreases alkaline phosphatase (ALP) activity, a marker of osteoblast differentiation. Three thrombin receptors have been identified, protease activated receptor (PAR)-1, PAR-3 and PAR-4; we have previously demonstrated that mouse osteoblasts express PAR-1 and PAR-4. The effect of thrombin on osteoblast proliferation and differentiation was studied to determine which of the thrombin receptors is responsible for the primary effects of thrombin. Primary mouse calvarial osteoblasts from PAR-1-null and wild-type mice, and synthetic peptides that specifically activate PAR-1 (TFFLR-NH2) and PAR-4 (AYPGKF-NH2) were used. Both the PAR-1-activating peptide and thrombin stimulated incorporation of 5-bromo-2'-deoxyuridine (two to four-fold, P < 0.001) and reduced alkaline phosphatase activity (approximately three-fold, P < 0.05) in cells from wild-type mice. The PAR-4-activating peptide, however, had no effect on either alkaline phosphatase activity or proliferation in these cells. Neither thrombin nor PAR-4-activating peptide was able to affect osteoblast proliferation or alkaline phosphatase activity in cells isolated from PAR-1-null mice. The results demonstrate ...Continue Reading
References
Mar 22, 1991·Cell·T K VuS R Coughlin
Oct 16, 1989·Biochemical and Biophysical Research Communications·D N TatakisR Dziak
Jan 1, 1987·Methods in Enzymology·T J MartinS A Livesey
Aug 12, 1986·Biochemistry·S R Stone, J Hofsteenge
Jun 6, 1996·Nature·A J ConnollyS R Coughlin
Jul 1, 1996·Journal of Cellular Physiology·A SuzukiY Oiso
Jun 14, 1996·The Journal of Biological Chemistry·D J LernerS R Coughlin
Apr 3, 1997·Nature·H IshiharaS R Coughlin
Jun 4, 1998·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·L A AbrahamE J Mackie
Aug 8, 1998·The International Journal of Biochemistry & Cell Biology·N R GoldsackG J Laurent
Aug 26, 1998·Nature·M L KahnS R Coughlin
Feb 19, 1999·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·M AbeH Kido
Aug 24, 1999·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·L A Abraham, E J MacKie
Sep 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·S R Coughlin
Jan 5, 2000·Bone·L A AbrahamE J Mackie
Jan 25, 2000·American Journal of Physiology. Lung Cellular and Molecular Physiology·I A AkersR J McAnulty
Apr 15, 2000·Nature·M Nakanishi-MatsuiS R Coughlin
Apr 26, 2000·The Journal of Biological Chemistry·T R FaruqiS R Coughlin
Jun 6, 2000·The Journal of Biological Chemistry·M J ShapiroS R Coughlin
Sep 5, 2001·Science·C T GriffinS R Coughlin
Feb 22, 2002·Experimental Cell Research·M R de NieseE J Mackie
Jan 11, 2003·The Journal of Biological Chemistry·Abdelkarim SabriSusan F Steinberg
Mar 11, 2003·IUBMB Life·E J MackieR N Pike
Oct 14, 2003·Bone·Charles N PagelEleanor J Mackie
Citations
Mar 4, 2005·The American Journal of Pathology·Shu Jun SongEleanor J Mackie
Jan 24, 2009·The Journal of Craniofacial Surgery·Kemal FindikciogluKenan Atabay
Aug 10, 2006·Biological Chemistry·Charles N PagelEleanor J Mackie
Feb 20, 2013·Journal of Molecular Endocrinology·S SivagurunathanE J Mackie
Mar 6, 2012·Biomaterials·Joung-Hwan OhKyung Mi Woo
Oct 7, 2009·Thrombosis Research·Tatsuya KurataKoji Suzuki
May 21, 2008·The International Journal of Biochemistry & Cell Biology·Kitipong UaesoontrachoonCharles N Pagel
Dec 13, 2006·Cytokine·G HardingG Hampson
Apr 14, 2015·Stem Cells·Melonie J StoranSusan K Nilsson
Jan 27, 2009·The Prostate·Xiaotun ZhangThomas K Takayama
Jan 27, 2006·Biomaterials·Gilles BluteauJérôme Guicheux
Sep 10, 2014·Arthritis & Rheumatology·Miriam T JacksonChristopher B Little
Sep 17, 2014·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Kaitlin ShenAaron Schindeler
May 16, 2009·Bone·Charles N PagelEleanor J Mackie
Sep 4, 2018·Cytoskeleton·Siddheshwari AdvaniJennifer L Ross
May 22, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sandra JastrzebskiJoseph A Lorenzo
Sep 11, 2014·Biological Chemistry·Yuma MaedaAtsufumi Kawabata
Aug 2, 2017·Journal of Dental Research·M M P AlvarezF D Nascimento
Jul 10, 2019·Stem Cells International·Emanuel Silva RovaiMarinella Holzhausen
Jan 19, 2021·Life Sciences·Jian SongZhuoli Zhu
Dec 29, 2020·Seminars in Thrombosis and Hemostasis·Hanshi Wang, Xizhuang Bai
Jun 13, 2021·Calcified Tissue International·Emily A LarsonRobert F Klein