PMID- 37069673 OWN - NLM STAT- MEDLINE DCOM- 20230419 LR - 20230421 IS - 1757-6512 (Electronic) IS - 1757-6512 (Linking) VI - 14 IP - 1 DP - 2023 Apr 17 TI - Low-intensity pulsed ultrasound promotes mesenchymal stem cell transplantation-based articular cartilage regeneration via inhibiting the TNF signaling pathway. PG - 93 LID - 10.1186/s13287-023-03296-6 [doi] LID - 93 AB - BACKGROUND: Mesenchymal stem cell (MSC) transplantation therapy is highly investigated for the regenerative repair of cartilage defects. Low-intensity pulsed ultrasound (LIPUS) has the potential to promote chondrogenic differentiation of MSCs. However, its underlying mechanism remains unclear. Here, we investigated the promoting effects and mechanisms underlying LIPUS stimulation on the chondrogenic differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs) and further evaluated its regenerative application value in articular cartilage defects in rats. METHODS: LIPUS was applied to stimulate cultured hUC-MSCs and C28/I2 cells in vitro. Immunofluorescence staining, qPCR analysis, and transcriptome sequencing were used to detect mature cartilage-related markers of gene and protein expression for a comprehensive evaluation of differentiation. Injured articular cartilage rat models were established for further hUC-MSC transplantation and LIPUS stimulation in vivo. Histopathology and H&E staining were used to evaluate the repair effects of the injured articular cartilage with LIPUS stimulation. RESULTS: The results showed that LIPUS stimulation with specific parameters effectively promoted the expression of mature cartilage-related genes and proteins, inhibited TNF-alpha gene expression in hUC-MSCs, and exhibited anti-inflammation in C28/I2 cells. In addition, the articular cartilage defects of rats were significantly repaired after hUC-MSC transplantation and LIPUS stimulation. CONCLUSIONS: Taken together, LIPUS stimulation could realize articular cartilage regeneration based on hUC-MSC transplantation due to the inhibition of the TNF signaling pathway, which is of clinical value for the relief of osteoarthritis. CI - (c) 2023. The Author(s). FAU - Chen, Yiming AU - Chen Y AD - Institute of Acoustics, School of Physics Science and Engineering, Tongji University, Shanghai, 200092, China. FAU - Yang, Huiyi AU - Yang H AD - Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital affiliated to Tongji University School of Medicine, Tongji University, Shanghai, 200065, China. FAU - Wang, Zhaojie AU - Wang Z AD - Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital affiliated to Tongji University School of Medicine, Tongji University, Shanghai, 200065, China. AD - School of Life Science and Technology, Tongji University, Shanghai, 200065, China. FAU - Zhu, Rongrong AU - Zhu R AD - Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital affiliated to Tongji University School of Medicine, Tongji University, Shanghai, 200065, China. AD - School of Life Science and Technology, Tongji University, Shanghai, 200065, China. FAU - Cheng, Liming AU - Cheng L AD - Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital affiliated to Tongji University School of Medicine, Tongji University, Shanghai, 200065, China. limingcheng@tongji.edu.cn. FAU - Cheng, Qian AU - Cheng Q AUID- ORCID: 0000-0003-3621-5743 AD - Institute of Acoustics, School of Physics Science and Engineering, Tongji University, Shanghai, 200092, China. q.cheng@tongji.edu.cn. AD - Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital affiliated to Tongji University School of Medicine, Tongji University, Shanghai, 200065, China. q.cheng@tongji.edu.cn. AD - Frontiers Science Center for Intelligent Autonomous Systems, Shanghai, 201210, China. q.cheng@tongji.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230417 PL - England TA - Stem Cell Res Ther JT - Stem cell research & therapy JID - 101527581 SB - IM MH - Rats MH - Humans MH - Animals MH - *Cartilage, Articular/pathology MH - *Mesenchymal Stem Cell Transplantation/methods MH - *Mesenchymal Stem Cells MH - Signal Transduction MH - Ultrasonic Waves PMC - PMC10111837 OTO - NOTNLM OT - Articular cartilage regeneration OT - Chondrogenic differentiation OT - Low-intensity pulsed ultrasound (LIPUS) OT - Mesenchymal stem cells (MSCs) OT - TNF signaling pathway COIS- The authors declare no competing interests. EDAT- 2023/04/19 06:00 MHDA- 2023/04/19 06:42 PMCR- 2023/04/17 CRDT- 2023/04/18 00:13 PHST- 2022/02/26 00:00 [received] PHST- 2023/03/22 00:00 [accepted] PHST- 2023/04/19 06:42 [medline] PHST- 2023/04/18 00:13 [entrez] PHST- 2023/04/19 06:00 [pubmed] PHST- 2023/04/17 00:00 [pmc-release] AID - 10.1186/s13287-023-03296-6 [pii] AID - 3296 [pii] AID - 10.1186/s13287-023-03296-6 [doi] PST - epublish SO - Stem Cell Res Ther. 2023 Apr 17;14(1):93. doi: 10.1186/s13287-023-03296-6.