Phospholipase C signaling activated by parathyroid hormone mediates the rapid osteoclastogenesis in the fracture healing of orchiectomized mice
Abstract Background The age-related osteoporosis is an increasing risk severely threatening the live quality of aged people. Human parathyroid hormone (hPTH) is applied to the therapy of osteoporosis successfully, however, the mechanism, especially the signaling pathway activated in the healing frac...
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| Format: | Article |
| Language: | English |
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BMC
2018-08-01
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| Series: | BMC Musculoskeletal Disorders |
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| Online Access: | http://link.springer.com/article/10.1186/s12891-018-2231-3 |
| _version_ | 1828312351618629632 |
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| author | Wei Li Liang Yuan Guojun Tong Youhua He Yue Meng Song Hao Jianting Chen Jun Guo Richard Bringhurst Dehong Yang |
| author_facet | Wei Li Liang Yuan Guojun Tong Youhua He Yue Meng Song Hao Jianting Chen Jun Guo Richard Bringhurst Dehong Yang |
| author_sort | Wei Li |
| collection | DOAJ |
| description | Abstract Background The age-related osteoporosis is an increasing risk severely threatening the live quality of aged people. Human parathyroid hormone (hPTH) is applied to the therapy of osteoporosis successfully, however, the mechanism, especially the signaling pathway activated in the healing fracture by PTH is still unknown. Methods The once daily injections of hPTH(1–34) and GR (1–34) (the PLC deficient analog) into the orchiectomized male mice with bone fracture, were started at the second day after fracture and lasted for 4 weeks. To explore the role of phospholipase C signaling in the androgen-deficient fracture healing, the fracture healing were evaluated via radiography, micro-CT, biomechanics testing, serum biochemistry, bone marrow cell culture and gene expression quantification. Results After two weeks of fracture, both peptides significantly increased bone mineral density (BMD), bone mass content (BMC) and bone volume (BV/TV) in the healing area. However, compared to hPTH(1–34), GR(1–34) induced more woven bones, the higher BMC and BMD, as well as the less serum TRAP and osteoclasts. After four weeks of treatment, the effects of hPTH(1–34) on fracture healing showed no difference to those of GR(1–34). Consistently, GR(1–34) induced the similar osteogenesis but less osteoclastogenesis under the ex vivo condition immediately after administration compared to hPTH(1–34), which was verified by the weaker activation of RANKL, NFATC1, TRAP and Cathepsin K in GR(1–34) treatment. Conclusion These results indicated that the PLC signaling activated by the intermittent injection of hPTH(1–34) leads to the bone resorption by rapidly activating the osteoclastogenesis in the fracture healing zone. |
| first_indexed | 2024-04-13T16:14:52Z |
| format | Article |
| id | doaj.art-486f605ba953463bb2ebd6af0e005c0a |
| institution | Directory Open Access Journal |
| issn | 1471-2474 |
| language | English |
| last_indexed | 2024-04-13T16:14:52Z |
| publishDate | 2018-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Musculoskeletal Disorders |
| spelling | doaj.art-486f605ba953463bb2ebd6af0e005c0a2022-12-22T02:40:06ZengBMCBMC Musculoskeletal Disorders1471-24742018-08-0119111210.1186/s12891-018-2231-3Phospholipase C signaling activated by parathyroid hormone mediates the rapid osteoclastogenesis in the fracture healing of orchiectomized miceWei Li0Liang Yuan1Guojun Tong2Youhua He3Yue Meng4Song Hao5Jianting Chen6Jun Guo7Richard Bringhurst8Dehong Yang9Department of Spinal Surgery, Nanfang Hospital, Southern Medical UniversityDepartment of Spinal Surgery, Nanfang Hospital, Southern Medical UniversityDepartment of Spinal Surgery, Nanfang Hospital, Southern Medical UniversityDepartment of Spinal Surgery, Nanfang Hospital, Southern Medical UniversityDepartment of Spinal Surgery, Nanfang Hospital, Southern Medical UniversityDepartment of Spinal Surgery, Nanfang Hospital, Southern Medical UniversityDepartment of Spinal Surgery, Nanfang Hospital, Southern Medical UniversityEndocrine Unit, Massachusetts General HospitalEndocrine Unit, Massachusetts General HospitalDepartment of Spinal Surgery, Nanfang Hospital, Southern Medical UniversityAbstract Background The age-related osteoporosis is an increasing risk severely threatening the live quality of aged people. Human parathyroid hormone (hPTH) is applied to the therapy of osteoporosis successfully, however, the mechanism, especially the signaling pathway activated in the healing fracture by PTH is still unknown. Methods The once daily injections of hPTH(1–34) and GR (1–34) (the PLC deficient analog) into the orchiectomized male mice with bone fracture, were started at the second day after fracture and lasted for 4 weeks. To explore the role of phospholipase C signaling in the androgen-deficient fracture healing, the fracture healing were evaluated via radiography, micro-CT, biomechanics testing, serum biochemistry, bone marrow cell culture and gene expression quantification. Results After two weeks of fracture, both peptides significantly increased bone mineral density (BMD), bone mass content (BMC) and bone volume (BV/TV) in the healing area. However, compared to hPTH(1–34), GR(1–34) induced more woven bones, the higher BMC and BMD, as well as the less serum TRAP and osteoclasts. After four weeks of treatment, the effects of hPTH(1–34) on fracture healing showed no difference to those of GR(1–34). Consistently, GR(1–34) induced the similar osteogenesis but less osteoclastogenesis under the ex vivo condition immediately after administration compared to hPTH(1–34), which was verified by the weaker activation of RANKL, NFATC1, TRAP and Cathepsin K in GR(1–34) treatment. Conclusion These results indicated that the PLC signaling activated by the intermittent injection of hPTH(1–34) leads to the bone resorption by rapidly activating the osteoclastogenesis in the fracture healing zone.http://link.springer.com/article/10.1186/s12891-018-2231-3Parathyroid hormoneFracture healingPhopholipase COsteoporosisOsteoclastogenesis |
| spellingShingle | Wei Li Liang Yuan Guojun Tong Youhua He Yue Meng Song Hao Jianting Chen Jun Guo Richard Bringhurst Dehong Yang Phospholipase C signaling activated by parathyroid hormone mediates the rapid osteoclastogenesis in the fracture healing of orchiectomized mice BMC Musculoskeletal Disorders Parathyroid hormone Fracture healing Phopholipase C Osteoporosis Osteoclastogenesis |
| title | Phospholipase C signaling activated by parathyroid hormone mediates the rapid osteoclastogenesis in the fracture healing of orchiectomized mice |
| title_full | Phospholipase C signaling activated by parathyroid hormone mediates the rapid osteoclastogenesis in the fracture healing of orchiectomized mice |
| title_fullStr | Phospholipase C signaling activated by parathyroid hormone mediates the rapid osteoclastogenesis in the fracture healing of orchiectomized mice |
| title_full_unstemmed | Phospholipase C signaling activated by parathyroid hormone mediates the rapid osteoclastogenesis in the fracture healing of orchiectomized mice |
| title_short | Phospholipase C signaling activated by parathyroid hormone mediates the rapid osteoclastogenesis in the fracture healing of orchiectomized mice |
| title_sort | phospholipase c signaling activated by parathyroid hormone mediates the rapid osteoclastogenesis in the fracture healing of orchiectomized mice |
| topic | Parathyroid hormone Fracture healing Phopholipase C Osteoporosis Osteoclastogenesis |
| url | http://link.springer.com/article/10.1186/s12891-018-2231-3 |
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