Sensory nerves directly promote osteoclastogenesis by secreting peptidyl-prolyl cis-trans isomerase D (Cyp40)
Abstract Given afferent functions, sensory nerves have recently been found to exert efferent effects and directly alter organ physiology. Additionally, several studies have highlighted the indirect but crucial role of sensory nerves in the regulation of the physiological function of osteoclasts. Non...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-12-01
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| Series: | Bone Research |
| Online Access: | https://doi.org/10.1038/s41413-023-00300-w |
| _version_ | 1797388476930326528 |
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| author | Junqin Li Bin Liu Hao Wu Shuaishuai Zhang Zhuowen Liang Shuo Guo Huijie Jiang Yue Song Xing Lei Yi Gao Pengzhen Cheng Donglin Li Jimeng Wang Yang Liu Di Wang Nazhi Zhan Jing Xu Lin Wang Guozhi Xiao Liu Yang GuoXian Pei |
| author_facet | Junqin Li Bin Liu Hao Wu Shuaishuai Zhang Zhuowen Liang Shuo Guo Huijie Jiang Yue Song Xing Lei Yi Gao Pengzhen Cheng Donglin Li Jimeng Wang Yang Liu Di Wang Nazhi Zhan Jing Xu Lin Wang Guozhi Xiao Liu Yang GuoXian Pei |
| author_sort | Junqin Li |
| collection | DOAJ |
| description | Abstract Given afferent functions, sensory nerves have recently been found to exert efferent effects and directly alter organ physiology. Additionally, several studies have highlighted the indirect but crucial role of sensory nerves in the regulation of the physiological function of osteoclasts. Nonetheless, evidence regarding the direct sensory nerve efferent influence on osteoclasts is lacking. In the current study, we found that high levels of efferent signals were transported directly from the sensory nerves into osteoclasts. Furthermore, sensory hypersensitivity significantly increased osteoclastic bone resorption, and sensory neurons (SNs) directly promoted osteoclastogenesis in an in vitro coculture system. Moreover, we screened a novel neuropeptide, Cyp40, using an isobaric tag for relative and absolute quantitation (iTRAQ). We observed that Cyp40 is the efferent signal from sensory nerves, and it plays a critical role in osteoclastogenesis via the aryl hydrocarbon receptor (AhR)-Ras/Raf-p-Erk-NFATc1 pathway. These findings revealed a novel mechanism regarding the influence of sensory nerves on bone regulation, i.e., a direct promoting effect on osteoclastogenesis by the secretion of Cyp40. Therefore, inhibiting Cyp40 could serve as a strategy to improve bone quality in osteoporosis and promote bone repair after bone injury. |
| first_indexed | 2024-03-08T22:41:23Z |
| format | Article |
| id | doaj.art-749b15643f1d4c03936ad7411cf66afb |
| institution | Directory Open Access Journal |
| issn | 2095-6231 |
| language | English |
| last_indexed | 2024-03-08T22:41:23Z |
| publishDate | 2023-12-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Bone Research |
| spelling | doaj.art-749b15643f1d4c03936ad7411cf66afb2023-12-17T12:09:40ZengNature Publishing GroupBone Research2095-62312023-12-0111111210.1038/s41413-023-00300-wSensory nerves directly promote osteoclastogenesis by secreting peptidyl-prolyl cis-trans isomerase D (Cyp40)Junqin Li0Bin Liu1Hao Wu2Shuaishuai Zhang3Zhuowen Liang4Shuo Guo5Huijie Jiang6Yue Song7Xing Lei8Yi Gao9Pengzhen Cheng10Donglin Li11Jimeng Wang12Yang Liu13Di Wang14Nazhi Zhan15Jing Xu16Lin Wang17Guozhi Xiao18Liu Yang19GuoXian Pei20Southern University of Science and Technology HospitalDepartment of Orthopedics, General Hospital of Northern Theater CommandDepartment of Orthopaedics, Xijing Hospital, Air Force Medical UniversityDepartment of Orthopaedics, Xijing Hospital, Air Force Medical UniversityDepartment of Orthopaedics, Xijing Hospital, Air Force Medical UniversityDepartment of Orthopaedics, Xijing Hospital, Air Force Medical UniversityLingtong Rehabilitation and Recuperation CenterDepartment of Orthopaedics, Xijing Hospital, Air Force Medical UniversityDepartment of Orthopedics, Linyi People’s HospitalSouthern University of Science and Technology HospitalDepartment of Orthopaedics, Xijing Hospital, Air Force Medical UniversityDepartment of Orthopaedics, Xijing Hospital, Air Force Medical UniversityDepartment of Orthopedics, 81 Army Hospital of the People’s Liberation ArmyDepartment of Anaesthesiology and Perioperative Medicine, Xijing Hospital, Fourth Military Medical UniversityDepartment of Orthopaedics, Xijing Hospital, Air Force Medical UniversitySchool of Medicine, Southern University of Science and TechnologySouthern University of Science and Technology HospitalSouthern University of Science and Technology HospitalSchool of Medicine, Southern University of Science and TechnologyDepartment of Orthopaedics, Xijing Hospital, Air Force Medical UniversitySouthern University of Science and Technology HospitalAbstract Given afferent functions, sensory nerves have recently been found to exert efferent effects and directly alter organ physiology. Additionally, several studies have highlighted the indirect but crucial role of sensory nerves in the regulation of the physiological function of osteoclasts. Nonetheless, evidence regarding the direct sensory nerve efferent influence on osteoclasts is lacking. In the current study, we found that high levels of efferent signals were transported directly from the sensory nerves into osteoclasts. Furthermore, sensory hypersensitivity significantly increased osteoclastic bone resorption, and sensory neurons (SNs) directly promoted osteoclastogenesis in an in vitro coculture system. Moreover, we screened a novel neuropeptide, Cyp40, using an isobaric tag for relative and absolute quantitation (iTRAQ). We observed that Cyp40 is the efferent signal from sensory nerves, and it plays a critical role in osteoclastogenesis via the aryl hydrocarbon receptor (AhR)-Ras/Raf-p-Erk-NFATc1 pathway. These findings revealed a novel mechanism regarding the influence of sensory nerves on bone regulation, i.e., a direct promoting effect on osteoclastogenesis by the secretion of Cyp40. Therefore, inhibiting Cyp40 could serve as a strategy to improve bone quality in osteoporosis and promote bone repair after bone injury.https://doi.org/10.1038/s41413-023-00300-w |
| spellingShingle | Junqin Li Bin Liu Hao Wu Shuaishuai Zhang Zhuowen Liang Shuo Guo Huijie Jiang Yue Song Xing Lei Yi Gao Pengzhen Cheng Donglin Li Jimeng Wang Yang Liu Di Wang Nazhi Zhan Jing Xu Lin Wang Guozhi Xiao Liu Yang GuoXian Pei Sensory nerves directly promote osteoclastogenesis by secreting peptidyl-prolyl cis-trans isomerase D (Cyp40) Bone Research |
| title | Sensory nerves directly promote osteoclastogenesis by secreting peptidyl-prolyl cis-trans isomerase D (Cyp40) |
| title_full | Sensory nerves directly promote osteoclastogenesis by secreting peptidyl-prolyl cis-trans isomerase D (Cyp40) |
| title_fullStr | Sensory nerves directly promote osteoclastogenesis by secreting peptidyl-prolyl cis-trans isomerase D (Cyp40) |
| title_full_unstemmed | Sensory nerves directly promote osteoclastogenesis by secreting peptidyl-prolyl cis-trans isomerase D (Cyp40) |
| title_short | Sensory nerves directly promote osteoclastogenesis by secreting peptidyl-prolyl cis-trans isomerase D (Cyp40) |
| title_sort | sensory nerves directly promote osteoclastogenesis by secreting peptidyl prolyl cis trans isomerase d cyp40 |
| url | https://doi.org/10.1038/s41413-023-00300-w |
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