دورية أكاديمية
أعرض في EDS

Prkd1 regulates the formation and repair of plasma membrane disruptions (PMD) in osteocytes.

التفاصيل البيبلوغرافية
العنوان: Prkd1 regulates the formation and repair of plasma membrane disruptions (PMD) in osteocytes.
المؤلفون: Tuladhar A; Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, GA, United States of America., Shaver JC; Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, GA, United States of America., McGee WA; Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, GA, United States of America., Yu K; Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, GA, United States of America., Dorn J; Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, GA, United States of America., Horne JL; Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, GA, United States of America., Alhamad DW; Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, GA, United States of America., Hagan ML; Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, GA, United States of America., Cooley MA; Department of Oral Biology and Diagnostic Sciences, Dental College of Georgia at Augusta University, Augusta, GA, United States of America., Zhong R; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia at AugustaUniversity, Augusta, GA, United States of America., Bollag W; Department of Physiology, Medical College of Georgia at Augusta University, Augusta, GA, United States of America; Charlie Norwood VA Medical Center, Augusta, GA, United States of America., Johnson M; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia at AugustaUniversity, Augusta, GA, United States of America., Hamrick MW; Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, GA, United States of America., McGee-Lawrence ME; Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, GA, United States of America. Electronic address: mmcgeelawrence@augusta.edu.
المصدر: Bone [Bone] 2024 Sep; Vol. 186, pp. 117147. Date of Electronic Publication: 2024 Jun 10.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Country of Publication: United States NLM ID: 8504048 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2763 (Electronic) Linking ISSN: 18732763 NLM ISO Abbreviation: Bone Subsets: MEDLINE
أسماء مطبوعة: Publication: New York : Elsevier Science
Original Publication: Elmsford, NY : Pergamon Press, c1985-
مواضيع طبية MeSH: Cell Membrane*/metabolism , Mice, Knockout* , Osteocytes*/metabolism , Osteocytes*/drug effects, Animals ; Mice ; Mechanotransduction, Cellular/drug effects ; Protein Kinase C/metabolism
مستخلص: We and others have seen that osteocytes sense high-impact osteogenic mechanical loading via transient plasma membrane disruptions (PMDs) which initiate downstream mechanotransduction. However, a PMD must be repaired for the cell to survive this wounding event. Previous work suggested that the protein Prkd1 (also known as PKCμ) may be a critical component of this PMD repair process, but the specific role of Prkd1 in osteocyte mechanobiology had not yet been tested. We treated MLO-Y4 osteocytes with Prkd1 inhibitors (Go6976, kbNB 142-70, staurosporine) and generated an osteocyte-targeted (Dmp1-Cre) Prkd1 conditional knockout (CKO) mouse. PMD repair rate was measured via laser wounding and FM1-43 dye uptake, PMD formation and post-wounding survival were assessed via fluid flow shear stress (50 dyn/cm 2 ), and in vitro osteocyte mechanotransduction was assessed via measurement of calcium signaling. To test the role of osteocyte Prkd1 in vivo, Prkd1 CKO and their wildtype (WT) littermates were subjected to 2 weeks of unilateral axial tibial loading and loading-induced changes in cortical bone mineral density, geometry, and formation were measured. Prkd1 inhibition or genetic deletion slowed osteocyte PMD repair rate and impaired post-wounding cell survival. These effects could largely be rescued by treating osteocytes with the FDA-approved synthetic copolymer Poloxamer 188 (P188), which was previously shown to facilitate membrane resealing and improve efficiency in the repair rate of PMD in skeletal muscle myocytes. In vivo, while both WT and Prkd1 CKO mice demonstrated anabolic responses to tibial loading, the magnitude of loading-induced increases in tibial BMD, cortical thickness, and periosteal mineralizing surface were blunted in Prkd1 CKO as compared to WT mice. Prkd1 CKO mice also tended to show a smaller relative difference in the number of osteocyte PMD in loaded limbs and showed greater lacunar vacancy, suggestive of impaired post-wounding osteocyte survival. While P188 treatment rescued loading-induced increases in BMD in the Prkd1 CKO mice, it surprisingly further suppressed loading-induced increases in cortical bone thickness and cortical bone formation. Taken together, these data suggest that Prkd1 may play a pivotal role in the regulation and repair of the PMD response in osteocytes and support the idea that PMD repair processes can be pharmacologically targeted to modulate downstream responses, but suggest limited utility of PMD repair-promoting P188 in improving bone anabolic responses to loading.
Competing Interests: Declaration of competing interest The authors state that they have no conflicts of interest.
(Copyright © 2024. Published by Elsevier Inc.)
References: Nature. 2005 Aug 18;436(7053):1025-9. (PMID: 16025101)
Proc Natl Acad Sci U S A. 1992 May 15;89(10):4524-8. (PMID: 1584787)
Biotechniques. 2012 Jun;52(6):361-73. (PMID: 22668415)
Curr Biol. 2009 Aug 25;19(16):1389-95. (PMID: 19631537)
Bone. 2021 Aug;149:115970. (PMID: 33892174)
J Endocrinol. 2019 Jul 1;:. (PMID: 31370004)
Neurochem Int. 2017 Oct;109:126-140. (PMID: 28433663)
Mol Pharmacol. 1992 Feb;41(2):387-92. (PMID: 1538715)
Nat Commun. 2011 Dec 20;2:597. (PMID: 22186893)
Br J Cancer. 2001 Dec 14;85(12):1987-97. (PMID: 11747344)
Am J Physiol Cell Physiol. 2003 Apr;284(4):C934-43. (PMID: 12477665)
Cell Commun Adhes. 2003 Jul-Dec;10(4-6):259-64. (PMID: 14681026)
Methods Mol Biol. 2012;816:67-81. (PMID: 22130923)
Adv Drug Deliv Rev. 2002 Sep 13;54(5):759-79. (PMID: 12204601)
Proc Natl Acad Sci U S A. 2012 Feb 28;109(9):3359-64. (PMID: 22331870)
J Biol Chem. 2005 Apr 22;280(16):16377-82. (PMID: 15710604)
Mol Cell Endocrinol. 2018 Oct 15;474:176-183. (PMID: 29530783)
Calcif Tissue Int. 2019 Feb;104(2):224-234. (PMID: 30357446)
Front Biosci. 2007 May 01;12:3757-67. (PMID: 17485336)
PLoS One. 2014 Mar 18;9(3):e91221. (PMID: 24642557)
Dev Cell. 2003 Apr;4(4):561-74. (PMID: 12689594)
J Bone Miner Res. 2013 Jan;28(1):2-17. (PMID: 23197339)
Immunol Lett. 2016 May;173:69-76. (PMID: 26987843)
Aging Cell. 2020 Jan;19(1):e13056. (PMID: 31743583)
J Cell Sci. 2015 Nov 15;128(22):4083-95. (PMID: 26459638)
Diabetes. 2011 Nov;60(11):3034-43. (PMID: 21940783)
J Orthop Res. 2020 Feb;38(2):233-252. (PMID: 31508836)
JACC Basic Transl Sci. 2016 Jun;1(4):224-234. (PMID: 27695713)
Biotechnol Appl Biochem. 1993 Dec;18(3):329-39. (PMID: 8297510)
Mol Ther Methods Clin Dev. 2015 Nov 11;2:15042. (PMID: 26623440)
FASEB J. 2010 Aug;24(8):2859-68. (PMID: 20371630)
Science. 2002 Jan 11;295(5553):325-8. (PMID: 11729268)
Biochem Biophys Res Commun. 2020 Jan 15;521(3):806-813. (PMID: 31708103)
J Bone Miner Res. 2011 Feb;26(2):277-85. (PMID: 20715178)
Bone. 2010 Nov;47(5):872-81. (PMID: 20713195)
Bone Res. 2020 Jun 8;8:23. (PMID: 32550039)
J Biol Chem. 2017 Jun 9;292(23):9523-9539. (PMID: 28408623)
Skelet Muscle. 2018 Oct 10;8(1):31. (PMID: 30305165)
Cell Mol Life Sci. 2018 Oct;75(20):3751-3770. (PMID: 30051163)
J Orthop Res. 2018 Feb;36(2):653-662. (PMID: 28755471)
Proc Natl Acad Sci U S A. 2023 May 2;120(18):e2219885120. (PMID: 37094151)
Mol Cell Endocrinol. 2018 Feb 5;461:22-31. (PMID: 28811183)
Neuromuscul Disord. 2006 Dec;16(12):855-64. (PMID: 17118658)
Am J Physiol Cell Physiol. 2020 Feb 1;318(2):C253-C262. (PMID: 31747313)
J Cell Sci. 1999 Mar;112 ( Pt 5):719-31. (PMID: 9973606)
Annu Rev Physiol. 2020 Feb 10;82:485-506. (PMID: 32040934)
Burns. 2004 Sep;30(6):539-47. (PMID: 15302418)
Front Physiol. 2020 Mar 31;11:299. (PMID: 32296345)
PLoS One. 2015 Aug 06;10(8):e0134832. (PMID: 26248188)
Curr Top Membr. 2016;77:67-96. (PMID: 26781830)
Ann Biomed Eng. 2017 Apr;45(4):1083-1092. (PMID: 27650939)
J Bone Miner Res. 2022 Feb;37(2):285-302. (PMID: 34747055)
J Biol Chem. 2003 May 16;278(20):17969-76. (PMID: 12637538)
J Bone Miner Res. 1997 Dec;12(12):2014-23. (PMID: 9421234)
FEBS Lett. 1996 Aug 26;392(2):77-80. (PMID: 8772178)
Int J Mol Sci. 2021 May 05;22(9):. (PMID: 34063028)
Biomech Model Mechanobiol. 2014 Jan;13(1):85-97. (PMID: 23567965)
Osteoporos Int. 2009 Jun;20(6):1027-31. (PMID: 19340507)
Curr Osteoporos Rep. 2017 Oct;15(5):401-411. (PMID: 28891009)
J Dent Res. 2007 Apr;86(4):320-5. (PMID: 17384025)
Connect Tissue Res. 2020 May-Jul;61(3-4):389-398. (PMID: 31931640)
Am J Physiol Cell Physiol. 2008 Jul;295(1):C146-50. (PMID: 18495816)
Neurosci Res. 2012 Feb;72(2):181-6. (PMID: 22044584)
Elife. 2018 Oct 16;7:. (PMID: 30324907)
J Pharmacol Exp Ther. 2001 Nov;299(2):483-93. (PMID: 11602658)
Plast Reconstr Surg. 2010 Jun;125(6):1651-1660. (PMID: 20517088)
J Orthop Translat. 2021 May 13;29:1-9. (PMID: 34036041)
BMC Cardiovasc Disord. 2011 May 16;11:20. (PMID: 21575230)
Recent Pat Biotechnol. 2012 Dec;6(3):200-11. (PMID: 23092436)
J Control Release. 2008 Sep 10;130(2):98-106. (PMID: 18534704)
Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13325-30. (PMID: 17673554)
J Control Release. 2003 Aug 28;91(1-2):75-83. (PMID: 12932639)
Mol Ther Methods Clin Dev. 2022 Dec 09;28:162-176. (PMID: 36654800)
معلومات مُعتمدة: S10 OD025177 United States OD NIH HHS
فهرسة مساهمة: Keywords: Mechanobiology; Mechanotransduction; Osteocyte; Osteogenic; Plasma membrane repair
المشرفين على المادة: EC 2.7.11.13 (Protein Kinase C)
EC 2.7.10.- (protein kinase D)
تواريخ الأحداث: Date Created: 20240612 Date Completed: 20240706 Latest Revision: 20240801
رمز التحديث: 20240801
مُعرف محوري في PubMed: PMC11246118
DOI: 10.1016/j.bone.2024.117147
PMID: 38866124
قاعدة البيانات: MEDLINE
الوصف
تدمد:1873-2763
DOI:10.1016/j.bone.2024.117147