PMID- 35457035 OWN - NLM STAT- MEDLINE DCOM- 20220426 LR - 20220716 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 23 IP - 8 DP - 2022 Apr 11 TI - Differential Nanoscale Topography Dedicates Osteocyte-Manipulated Osteogenesis via Regulation of the TGF-beta Signaling Pathway. LID - 10.3390/ijms23084212 [doi] LID - 4212 AB - Osteocytes function as the master orchestrator of bone remodeling activity in the telophase of osseointegration. However, most contemporary studies focus on the manipulation of osteoblast and/or osteoclast functionality via implant surface engineering, which neglects the pivotal role of osteocytes in de novo bone formation. It is confirmative that osteocyte processes extend directly to the implant surface, but whether the surface physicochemical properties can affect the functionality of osteocytes and determine the fate of the osseointegration in the final remodeling stage remains to be determined. Titania nanotube arrays (NTAs) with distinct diameters were fabricated to investigate the relationship between the nanoscale topography and the functionality of osteocytes. In vitro results pinpointed that NTA with a diameter of 15 nm (NTA-15) significantly promote osteogenesis of osteocytes via the enhancement of spreading, proliferation, and mineralization. The osteocyte transcriptome of each group further revealed that the TGF-beta signaling pathway plays a pivotal role in osteocyte-mediated osteogenesis. The in vivo study definitely mirrored the aforementioned results, that NTA-15 significantly promotes bone formation around the implant. Consequently, nanoscaled topography-induced osteocyte functionality is important in late osseointegration. This suggests that surface designs targeting osteocytes may, therefore, be a potential approach to solving the aseptic loosening of the implant, and thus strengthen osseointegration. FAU - Cui, Jingyuan AU - Cui J AD - Key Laboratory for Ultrafine Materials of Ministry of Education, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China. AD - Frontiers Science Center for Materiobiology and Dynamic Chemistry, College of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China. FAU - Yang, Yaru AU - Yang Y AD - College of Materials and Textile Engineering, Jiaxing University, Jiaxing 314001, China. FAU - Chen, Peiru AU - Chen P AD - State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Institute of Lifeomics, Beijing 102206, China. FAU - Hang, Ruiqiang AU - Hang R AD - Shanxi Key Laboratory of Biomedical Metal Materials, College of Materials Science and Engineering, Taiyuan University of Technology, Taiyuan 030024, China. FAU - Xiao, Yin AU - Xiao Y AUID- ORCID: 0000-0003-1785-3491 AD - Australia-China Centre for Tissue Engineering and Regenerative Medicine, Queensland University of Technology, Brisbane, QLD 4000, Australia. FAU - Liu, Xueting AU - Liu X AD - Key Laboratory for Ultrafine Materials of Ministry of Education, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China. FAU - Zhang, Lixin AU - Zhang L AD - Key Laboratory for Ultrafine Materials of Ministry of Education, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China. FAU - Sun, Hui AU - Sun H AD - Department of Orthopedics, Shanghai Jiaotong University School of Medicine, Shanghai 200233, China. FAU - Bai, Long AU - Bai L AUID- ORCID: 0000-0002-4757-746X AD - Key Laboratory for Ultrafine Materials of Ministry of Education, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China. AD - Frontiers Science Center for Materiobiology and Dynamic Chemistry, College of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China. LA - eng GR - 81901898/National Natural Science Foundation of China/ GR - 2019M661404/China Postdoctoral Science Foundation/ GR - 2020T130192/China Postdoctoral Science Foundation/ PT - Journal Article DEP - 20220411 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Transforming Growth Factor beta) SB - IM MH - Osteoblasts/metabolism MH - *Osteocytes/metabolism MH - *Osteogenesis MH - Signal Transduction MH - Transforming Growth Factor beta/metabolism PMC - PMC9027032 OTO - NOTNLM OT - TGF-beta OT - nanoscale OT - osseointegration OT - osteocyte OT - osteogenesis COIS- The authors declare no conflict of interest. EDAT- 2022/04/24 06:00 MHDA- 2022/04/27 06:00 PMCR- 2022/04/11 CRDT- 2022/04/23 01:11 PHST- 2022/02/03 00:00 [received] PHST- 2022/03/31 00:00 [revised] PHST- 2022/04/07 00:00 [accepted] PHST- 2022/04/23 01:11 [entrez] PHST- 2022/04/24 06:00 [pubmed] PHST- 2022/04/27 06:00 [medline] PHST- 2022/04/11 00:00 [pmc-release] AID - ijms23084212 [pii] AID - ijms-23-04212 [pii] AID - 10.3390/ijms23084212 [doi] PST - epublish SO - Int J Mol Sci. 2022 Apr 11;23(8):4212. doi: 10.3390/ijms23084212.