Hormone sensitive lipase ablation promotes bone regeneration.

Autor: Shen WJ; Division of Endocrinology, Gerontology, and Metabolism, Stanford University, Stanford, CA, USA; Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA., Still Ii C; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA., Han L; Division of Endocrinology, Gerontology, and Metabolism, Stanford University, Stanford, CA, USA; Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA., Yang P; Division of Endocrinology, Gerontology, and Metabolism, Stanford University, Stanford, CA, USA; Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA., Chen J; Division of Endocrinology, Gerontology, and Metabolism, Stanford University, Stanford, CA, USA; Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA., Wosczyna M; Department of Neurology and Neurological Sciences, Stanford School of Medicine, Stanford, CA, USA., Salmon BJR; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA, USA., Perez KC; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA, USA., Li J; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA, USA., Cuevas PL; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA, USA., Liu B; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA, USA., Azhar S; Division of Endocrinology, Gerontology, and Metabolism, Stanford University, Stanford, CA, USA; Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA., Helms J; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA, USA., Qi LS; Department of Bioengineering, Stanford University, Stanford, CA, USA; Sarafan ChEM-H, Stanford University, Stanford, CA, USA; Chan Zuckerberg Biohub, San Francisco, Stanford, CA, USA. Electronic address: slqi@stanford.edu., Kraemer FB; Division of Endocrinology, Gerontology, and Metabolism, Stanford University, Stanford, CA, USA; Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA; Stanford Diabetes Research Center, Stanford, CA, USA. Electronic address: fbk@stanford.edu.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2022 Sep 01; Vol. 1868 (9), pp. 166449. Date of Electronic Publication: 2022 May 23.
DOI: 10.1016/j.bbadis.2022.166449
Abstrakt: There is an inverse relationship between the differentiation of mesenchymal stem cells (MSCs) along either an adipocyte or osteoblast lineage, with lineage differentiation known to be mediated by transcription factors PPARγ and Runx2, respectively. Endogenous ligands for PPARγ are generated during the hydrolysis of triacylglycerols to fatty acids through the actions of lipases such as hormone sensitive lipase (HSL). To examine whether reduced production of endogenous PPARγ ligands would influence bone regeneration, we examined the effects of HSL knockout on fracture repair in mice using a tibial mono-cortical defect as a model. We found an improved rate of fracture repair in HSL-ko mice documented by serial μCT and bone histomorphometry compared to wild-type (WT) mice. Similarly, accelerated rates of bone regeneration were observed with a calvarial model where implantation of bone grafts from HSL-ko mice accelerated bone regeneration at the injury site. Further analysis revealed improved MSC differentiation down osteoblast and chondrocyte lineage with inhibition of HSL. MSC recruitment to the injury site was greater in HSL-ko mice than WT. Finally, we used single cell RNAseq to understand the osteoimmunological differences between WT and HSL-ko mice and found changes in the pre-osteoclast population. Our study shows HSL-ko mice as an interesting model to study improvements to bone injury repair. Furthermore, our study highlights the potential importance of pre-osteoclasts and osteoclasts in bone repair.
(Copyright © 2022. Published by Elsevier B.V.)
Databáze: MEDLINE
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