Connexin hemichannels with prostaglandin release in anabolic function of bone to mechanical loading
Mechanical stimulation, such as physical exercise, is essential for bone formation and health. Here, we demonstrate the critical role of osteocytic Cx43 hemichannels in anabolic function of bone in response to mechanical loading. Two transgenic mouse models, R76W and Δ130–136, expressing dominant-ne...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-02-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/74365 |
| _version_ | 1818026388798570496 |
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| author | Dezhi Zhao Manuel A Riquelme Teja Guda Chao Tu Huiyun Xu Sumin Gu Jean X Jiang |
| author_facet | Dezhi Zhao Manuel A Riquelme Teja Guda Chao Tu Huiyun Xu Sumin Gu Jean X Jiang |
| author_sort | Dezhi Zhao |
| collection | DOAJ |
| description | Mechanical stimulation, such as physical exercise, is essential for bone formation and health. Here, we demonstrate the critical role of osteocytic Cx43 hemichannels in anabolic function of bone in response to mechanical loading. Two transgenic mouse models, R76W and Δ130–136, expressing dominant-negative Cx43 mutants in osteocytes were adopted. Mechanical loading of tibial bone increased cortical bone mass and mechanical properties in wild-type and gap junction-impaired R76W mice through increased PGE2, endosteal osteoblast activity, and decreased sclerostin. These anabolic responses were impeded in gap junction/hemichannel-impaired Δ130–136 mice and accompanied by increased endosteal osteoclast activity. Specific inhibition of Cx43 hemichannels by Cx43(M1) antibody suppressed PGE2 secretion and impeded loading-induced endosteal osteoblast activity, bone formation and anabolic gene expression. PGE2 administration rescued the osteogenic response to mechanical loading impeded by impaired hemichannels. Together, osteocytic Cx43 hemichannels could be a potential new therapeutic target for treating bone loss and osteoporosis. |
| first_indexed | 2024-12-10T04:31:13Z |
| format | Article |
| id | doaj.art-5ed3694c2b8a48229893da574febaf5e |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T04:31:13Z |
| publishDate | 2022-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-5ed3694c2b8a48229893da574febaf5e2022-12-22T02:02:09ZengeLife Sciences Publications LtdeLife2050-084X2022-02-011110.7554/eLife.74365Connexin hemichannels with prostaglandin release in anabolic function of bone to mechanical loadingDezhi Zhao0https://orcid.org/0000-0001-8249-8743Manuel A Riquelme1https://orcid.org/0000-0002-1915-0434Teja Guda2Chao Tu3Huiyun Xu4Sumin Gu5Jean X Jiang6https://orcid.org/0000-0002-2185-5716Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, United States; School of Life Sciences, Northwestern Polytechnical University, Xian, ChinaDepartment of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, United StatesDepartment of Biomedical Engineering and Chemical Engineering, University of Texas at San Antonio, San Antonio, United StatesDepartment of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, United States; Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, ChinaSchool of Life Sciences, Northwestern Polytechnical University, Xian, ChinaDepartment of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, United StatesDepartment of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, United StatesMechanical stimulation, such as physical exercise, is essential for bone formation and health. Here, we demonstrate the critical role of osteocytic Cx43 hemichannels in anabolic function of bone in response to mechanical loading. Two transgenic mouse models, R76W and Δ130–136, expressing dominant-negative Cx43 mutants in osteocytes were adopted. Mechanical loading of tibial bone increased cortical bone mass and mechanical properties in wild-type and gap junction-impaired R76W mice through increased PGE2, endosteal osteoblast activity, and decreased sclerostin. These anabolic responses were impeded in gap junction/hemichannel-impaired Δ130–136 mice and accompanied by increased endosteal osteoclast activity. Specific inhibition of Cx43 hemichannels by Cx43(M1) antibody suppressed PGE2 secretion and impeded loading-induced endosteal osteoblast activity, bone formation and anabolic gene expression. PGE2 administration rescued the osteogenic response to mechanical loading impeded by impaired hemichannels. Together, osteocytic Cx43 hemichannels could be a potential new therapeutic target for treating bone loss and osteoporosis.https://elifesciences.org/articles/74365connexinsosteocytemechanical loadinghemichannel |
| spellingShingle | Dezhi Zhao Manuel A Riquelme Teja Guda Chao Tu Huiyun Xu Sumin Gu Jean X Jiang Connexin hemichannels with prostaglandin release in anabolic function of bone to mechanical loading eLife connexins osteocyte mechanical loading hemichannel |
| title | Connexin hemichannels with prostaglandin release in anabolic function of bone to mechanical loading |
| title_full | Connexin hemichannels with prostaglandin release in anabolic function of bone to mechanical loading |
| title_fullStr | Connexin hemichannels with prostaglandin release in anabolic function of bone to mechanical loading |
| title_full_unstemmed | Connexin hemichannels with prostaglandin release in anabolic function of bone to mechanical loading |
| title_short | Connexin hemichannels with prostaglandin release in anabolic function of bone to mechanical loading |
| title_sort | connexin hemichannels with prostaglandin release in anabolic function of bone to mechanical loading |
| topic | connexins osteocyte mechanical loading hemichannel |
| url | https://elifesciences.org/articles/74365 |
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