Low-Intensity Pulsed Ultrasound Modulates RhoA/ROCK Signaling of Rat Mandibular Bone Marrow Mesenchymal Stem Cells to Rescue Their Damaged Cytoskeletal Organization and Cell Biological Function Induced by Radiation
Osteoradionecrosis of the jaw (ORNJ) is an infrequent yet potentially devastating complication of head and neck radiation therapy. Low-intensity pulsed ultrasound (LIPUS) has been widely accepted as a promising method for the successful management of ORNJ, but the mechanism remains unclear. In this...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-01-01
|
| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2020/8863577 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832551250614288384 |
|---|---|
| author | Rong Zhang Zhaoling Wang Guoxiong Zhu Gaoyi Wu Qingyuan Guo Hongchen Liu Lei Chen |
| author_facet | Rong Zhang Zhaoling Wang Guoxiong Zhu Gaoyi Wu Qingyuan Guo Hongchen Liu Lei Chen |
| author_sort | Rong Zhang |
| collection | DOAJ |
| description | Osteoradionecrosis of the jaw (ORNJ) is an infrequent yet potentially devastating complication of head and neck radiation therapy. Low-intensity pulsed ultrasound (LIPUS) has been widely accepted as a promising method for the successful management of ORNJ, but the mechanism remains unclear. In this study, the effects of LIPUS on cytoskeletal reorganization, cell viability, and osteogenic differentiation capacity of rat mandible-derived bone marrow mesenchymal stem cells (M-BMMSCs) induced by radiation were determined by immunofluorescence staining, CCK-8 cell proliferation assay, quantification of alkaline phosphatase (ALP) activity, alizarin red staining, and real-time RT-PCR, respectively. Moreover, the involvement of the RhoA/ROCK signaling pathway underlying this process was investigated via western blot analysis. We found that radiation induced significant damage to the cytoskeleton, cell viability, and osteogenic differentiation capacity of M-BMMSCs and downregulated their expression of RhoA, ROCK, and vinculin while increasing FAK expression. LIPUS treatment effectively rescued the disordered cytoskeleton and redistributed vinculin. Furthermore, the cell viability and osteogenic differentiation capacity were also significantly recovered. More importantly, it could reverse the aberrant expression of the key molecules induced by radiation. Inhibition of RhoA/ROCK signaling remarkably aggravated the inhibitory effect of radiation and attenuated the therapeutic effect of LIPUS. In the light of these findings, the RhoA/ROCK signaling pathway might be a promising target for modifying the therapeutic effect of LIPUS on osteoradionecrosis. |
| format | Article |
| id | doaj-art-4fe6923c6bd64910a91e6e2770bc68ab |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-4fe6923c6bd64910a91e6e2770bc68ab2025-02-03T06:04:36ZengWileyStem Cells International1687-966X1687-96782020-01-01202010.1155/2020/88635778863577Low-Intensity Pulsed Ultrasound Modulates RhoA/ROCK Signaling of Rat Mandibular Bone Marrow Mesenchymal Stem Cells to Rescue Their Damaged Cytoskeletal Organization and Cell Biological Function Induced by RadiationRong Zhang0Zhaoling Wang1Guoxiong Zhu2Gaoyi Wu3Qingyuan Guo4Hongchen Liu5Lei Chen6Institute of Stomatology & Oral Maxilla Facial Key Laboratory, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing 100853, ChinaDepartment of Stomatology, No.960 Hospital of PLA, No. 25 Shifan Road, Jinan, Shandong Province 250000, ChinaDepartment of Stomatology, No.960 Hospital of PLA, No. 25 Shifan Road, Jinan, Shandong Province 250000, ChinaDepartment of Stomatology, No.960 Hospital of PLA, No. 25 Shifan Road, Jinan, Shandong Province 250000, ChinaDepartment of Stomatology, Qingdao Municipal Hospital Group, Qingdao University, Qingdao, Shandong Province 266011, ChinaInstitute of Stomatology & Oral Maxilla Facial Key Laboratory, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing 100853, ChinaDepartment of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, No. 44-1 Wenhua Road West, Jinan, Shandong Province 250012, ChinaOsteoradionecrosis of the jaw (ORNJ) is an infrequent yet potentially devastating complication of head and neck radiation therapy. Low-intensity pulsed ultrasound (LIPUS) has been widely accepted as a promising method for the successful management of ORNJ, but the mechanism remains unclear. In this study, the effects of LIPUS on cytoskeletal reorganization, cell viability, and osteogenic differentiation capacity of rat mandible-derived bone marrow mesenchymal stem cells (M-BMMSCs) induced by radiation were determined by immunofluorescence staining, CCK-8 cell proliferation assay, quantification of alkaline phosphatase (ALP) activity, alizarin red staining, and real-time RT-PCR, respectively. Moreover, the involvement of the RhoA/ROCK signaling pathway underlying this process was investigated via western blot analysis. We found that radiation induced significant damage to the cytoskeleton, cell viability, and osteogenic differentiation capacity of M-BMMSCs and downregulated their expression of RhoA, ROCK, and vinculin while increasing FAK expression. LIPUS treatment effectively rescued the disordered cytoskeleton and redistributed vinculin. Furthermore, the cell viability and osteogenic differentiation capacity were also significantly recovered. More importantly, it could reverse the aberrant expression of the key molecules induced by radiation. Inhibition of RhoA/ROCK signaling remarkably aggravated the inhibitory effect of radiation and attenuated the therapeutic effect of LIPUS. In the light of these findings, the RhoA/ROCK signaling pathway might be a promising target for modifying the therapeutic effect of LIPUS on osteoradionecrosis.http://dx.doi.org/10.1155/2020/8863577 |
| spellingShingle | Rong Zhang Zhaoling Wang Guoxiong Zhu Gaoyi Wu Qingyuan Guo Hongchen Liu Lei Chen Low-Intensity Pulsed Ultrasound Modulates RhoA/ROCK Signaling of Rat Mandibular Bone Marrow Mesenchymal Stem Cells to Rescue Their Damaged Cytoskeletal Organization and Cell Biological Function Induced by Radiation Stem Cells International |
| title | Low-Intensity Pulsed Ultrasound Modulates RhoA/ROCK Signaling of Rat Mandibular Bone Marrow Mesenchymal Stem Cells to Rescue Their Damaged Cytoskeletal Organization and Cell Biological Function Induced by Radiation |
| title_full | Low-Intensity Pulsed Ultrasound Modulates RhoA/ROCK Signaling of Rat Mandibular Bone Marrow Mesenchymal Stem Cells to Rescue Their Damaged Cytoskeletal Organization and Cell Biological Function Induced by Radiation |
| title_fullStr | Low-Intensity Pulsed Ultrasound Modulates RhoA/ROCK Signaling of Rat Mandibular Bone Marrow Mesenchymal Stem Cells to Rescue Their Damaged Cytoskeletal Organization and Cell Biological Function Induced by Radiation |
| title_full_unstemmed | Low-Intensity Pulsed Ultrasound Modulates RhoA/ROCK Signaling of Rat Mandibular Bone Marrow Mesenchymal Stem Cells to Rescue Their Damaged Cytoskeletal Organization and Cell Biological Function Induced by Radiation |
| title_short | Low-Intensity Pulsed Ultrasound Modulates RhoA/ROCK Signaling of Rat Mandibular Bone Marrow Mesenchymal Stem Cells to Rescue Their Damaged Cytoskeletal Organization and Cell Biological Function Induced by Radiation |
| title_sort | low intensity pulsed ultrasound modulates rhoa rock signaling of rat mandibular bone marrow mesenchymal stem cells to rescue their damaged cytoskeletal organization and cell biological function induced by radiation |
| url | http://dx.doi.org/10.1155/2020/8863577 |
| work_keys_str_mv | AT rongzhang lowintensitypulsedultrasoundmodulatesrhoarocksignalingofratmandibularbonemarrowmesenchymalstemcellstorescuetheirdamagedcytoskeletalorganizationandcellbiologicalfunctioninducedbyradiation AT zhaolingwang lowintensitypulsedultrasoundmodulatesrhoarocksignalingofratmandibularbonemarrowmesenchymalstemcellstorescuetheirdamagedcytoskeletalorganizationandcellbiologicalfunctioninducedbyradiation AT guoxiongzhu lowintensitypulsedultrasoundmodulatesrhoarocksignalingofratmandibularbonemarrowmesenchymalstemcellstorescuetheirdamagedcytoskeletalorganizationandcellbiologicalfunctioninducedbyradiation AT gaoyiwu lowintensitypulsedultrasoundmodulatesrhoarocksignalingofratmandibularbonemarrowmesenchymalstemcellstorescuetheirdamagedcytoskeletalorganizationandcellbiologicalfunctioninducedbyradiation AT qingyuanguo lowintensitypulsedultrasoundmodulatesrhoarocksignalingofratmandibularbonemarrowmesenchymalstemcellstorescuetheirdamagedcytoskeletalorganizationandcellbiologicalfunctioninducedbyradiation AT hongchenliu lowintensitypulsedultrasoundmodulatesrhoarocksignalingofratmandibularbonemarrowmesenchymalstemcellstorescuetheirdamagedcytoskeletalorganizationandcellbiologicalfunctioninducedbyradiation AT leichen lowintensitypulsedultrasoundmodulatesrhoarocksignalingofratmandibularbonemarrowmesenchymalstemcellstorescuetheirdamagedcytoskeletalorganizationandcellbiologicalfunctioninducedbyradiation |