دورية أكاديمية
Connexin 43 Channels in Osteocytes Are Necessary for Bone Mass and Skeletal Muscle Function in Aged Male Mice
العنوان: | Connexin 43 Channels in Osteocytes Are Necessary for Bone Mass and Skeletal Muscle Function in Aged Male Mice |
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المؤلفون: | Guobin Li, Lan Zhang, Zhe Lu, Baoqiang Yang, Hui Yang, Peng Shang, Jean X. Jiang, Dong’en Wang, Huiyun Xu |
المصدر: | International Journal of Molecular Sciences, Vol 23, Iss 21, p 13506 (2022) |
بيانات النشر: | MDPI AG, 2022. |
سنة النشر: | 2022 |
المجموعة: | LCC:Biology (General) LCC:Chemistry |
مصطلحات موضوعية: | osteocytes, hemichannels, gap junctions, bone-muscle crosstalk, aging, Biology (General), QH301-705.5, Chemistry, QD1-999 |
الوصف: | Osteoporosis and sarcopenia (termed “Osteosarcopenia”), the twin-aging diseases, are major contributors to reduced bone mass and muscle weakness in the elderly population. Connexin 43 (Cx43) in osteocytes has been previously reported to play vital roles in bone homeostasis and muscle function in mature mice. The Cx43-formed gap junctions (GJs) and hemichannels (HCs) in osteocytes are important portals for the exchange of small molecules in cell-to-cell and cell-to-extracellular matrix, respectively. However, the roles of Cx43-based GJs and HCs in both bone and muscle aging are still unclear. Here, we used two transgenic mouse models with overexpression of the dominant negative Cx43 mutants primarily in osteocytes driven by the 10-kb Dmp1 promoter, R76W mice (inhibited gap junctions but enhanced hemichannels) and Δ130–136 mice (both gap junction and hemichannels are inhibited), to determine the actions of Cx43-based hemichannels (HCs) and gap junctions (GJs) in the regulation of bone and skeletal muscle from aged mice (18 months) as compared with those from adult mice (10 months). We demonstrated that enhancement of Cx43 HCs reduces bone mass due to increased osteoclast surfaces while the impairment of Cx43 HCs increases osteocyte apoptosis in aged mice caused by reduced PGE2 levels. Furthermore, altered mitochondrial homeostasis with reduced expression of Sirt-1, OPA-1, and Drp-1 resulted in excessive ROS level in muscle soleus (SL) of aged transgenic mice. In vitro, the impairment of Cx43 HCs in osteocytes from aged mice also promoted muscle collagen synthesis through activation of TGFβ/smad2/3 signaling because of reduced PGE2 levels in the PO CM. These findings indicate that the enhancement of Cx43 HCs while GJs are inhibited reduces bone mass, and the impairment of Cx43 HCs inhibits PGE2 level in osteocytes and this reduction promotes muscle collagen synthesis in skeletal muscle through activation of TGFβ/smad2/3 signaling, which together with increased ROS level contributes to reduced muscle force in aged mice. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 23211350 1422-0067 1661-6596 |
Relation: | https://www.mdpi.com/1422-0067/23/21/13506; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067 |
DOI: | 10.3390/ijms232113506 |
URL الوصول: | https://doaj.org/article/7220bb4457c643d3824daac08de0a2cd |
رقم الأكسشن: | edsdoj.7220bb4457c643d3824daac08de0a2cd |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 23211350 14220067 16616596 |
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DOI: | 10.3390/ijms232113506 |