Orchestration of energy metabolism and osteogenesis by Mg2+ facilitates low-dose BMP-2-driven regeneration
The clinical application of bone morphogenetic protein-2 (BMP-2) is limited by several factors, including ineffectiveness at low doses and severe adverse effects at high doses. To address these efficacy and safety limitations, we explored whether orchestration of energy metabolism and osteogenesis b...
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KeAi Communications Co., Ltd.
2022-12-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X22001396 |
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| author | Sihan Lin Shi Yin Junfeng Shi Guangzheng Yang Xutao Wen Wenjie Zhang Mingliang Zhou Xinquan Jiang |
| author_facet | Sihan Lin Shi Yin Junfeng Shi Guangzheng Yang Xutao Wen Wenjie Zhang Mingliang Zhou Xinquan Jiang |
| author_sort | Sihan Lin |
| collection | DOAJ |
| description | The clinical application of bone morphogenetic protein-2 (BMP-2) is limited by several factors, including ineffectiveness at low doses and severe adverse effects at high doses. To address these efficacy and safety limitations, we explored whether orchestration of energy metabolism and osteogenesis by magnesium ion (Mg2+) could reduce the dose and thereby improve the safety of BMP-2. Our results demonstrated that rapid metabolic activation triggered by BMP-2 was indispensable for subsequent osteogenesis. Moreover, inadequate metabolic stimulation was shown to be responsible for the ineffectiveness of low-dose BMP-2. Next, we identified that Mg2+, as an ''energy propellant'', substantially increased cellular bioenergetic levels to support the osteogenesis via the Akt-glycolysis-Mrs2-mitochondrial axis, and consequently enhanced the osteoinductivity of BMP-2. Based on the mechanistic discovery, microgel composite hydrogels were fabricated as low-dose BMP-2/Mg2+ codelivery system through microfluidic and 3D printing technologies. An in vivo study further confirmed that rapid and robust bone regeneration was induced by the codelivery system. Collectively, these results suggest that this bioenergetic-driven, cost-effective, low-dose BMP-2-based strategy has substantial potential for bone repair. |
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| last_indexed | 2025-03-22T05:32:56Z |
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| spelling | doaj.art-50d238f7b6c94e2e8d0614d353113cfd2024-04-26T20:40:33ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2022-12-0118116127Orchestration of energy metabolism and osteogenesis by Mg2+ facilitates low-dose BMP-2-driven regenerationSihan Lin0Shi Yin1Junfeng Shi2Guangzheng Yang3Xutao Wen4Wenjie Zhang5Mingliang Zhou6Xinquan Jiang7Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; College of Stomatology, Shanghai JiaoTong University, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; National Center for Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; National Clinical Research Center for Oral Diseases, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; Shanghai Key Laboratory of Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; Shanghai Engineering Research Center of Advanced Dental Technology and Materials, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of ChinaDepartment of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; College of Stomatology, Shanghai JiaoTong University, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; National Center for Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; National Clinical Research Center for Oral Diseases, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; Shanghai Key Laboratory of Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; Shanghai Engineering Research Center of Advanced Dental Technology and Materials, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of ChinaDepartment of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; College of Stomatology, Shanghai JiaoTong University, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; National Center for Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; National Clinical Research Center for Oral Diseases, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; Shanghai Key Laboratory of Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; Shanghai Engineering Research Center of Advanced Dental Technology and Materials, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of ChinaDepartment of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; College of Stomatology, Shanghai JiaoTong University, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; National Center for Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; National Clinical Research Center for Oral Diseases, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; Shanghai Key Laboratory of Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; Shanghai Engineering Research Center of Advanced Dental Technology and Materials, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of ChinaDepartment of Oral and Maxillofacial Surgery, College and Hospital of Stomatology, Guangxi Medical University, No. 10 Shuangyong Road, Qingxiu District, Nanning, Guangxi, 530021, People's Republic of ChinaDepartment of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; College of Stomatology, Shanghai JiaoTong University, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; National Center for Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; National Clinical Research Center for Oral Diseases, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; Shanghai Key Laboratory of Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; Shanghai Engineering Research Center of Advanced Dental Technology and Materials, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of ChinaDepartment of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; College of Stomatology, Shanghai JiaoTong University, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; National Center for Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; National Clinical Research Center for Oral Diseases, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; Shanghai Key Laboratory of Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; Shanghai Engineering Research Center of Advanced Dental Technology and Materials, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; Corresponding author. Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, No.639 Zhizaoju Road, Shanghai, 200011, People's Republic of China.Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; College of Stomatology, Shanghai JiaoTong University, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; National Center for Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; National Clinical Research Center for Oral Diseases, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; Shanghai Key Laboratory of Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; Shanghai Engineering Research Center of Advanced Dental Technology and Materials, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China; Corresponding author. Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, No.639 Zhizaoju Road, Shanghai, 200011, People's Republic of China.The clinical application of bone morphogenetic protein-2 (BMP-2) is limited by several factors, including ineffectiveness at low doses and severe adverse effects at high doses. To address these efficacy and safety limitations, we explored whether orchestration of energy metabolism and osteogenesis by magnesium ion (Mg2+) could reduce the dose and thereby improve the safety of BMP-2. Our results demonstrated that rapid metabolic activation triggered by BMP-2 was indispensable for subsequent osteogenesis. Moreover, inadequate metabolic stimulation was shown to be responsible for the ineffectiveness of low-dose BMP-2. Next, we identified that Mg2+, as an ''energy propellant'', substantially increased cellular bioenergetic levels to support the osteogenesis via the Akt-glycolysis-Mrs2-mitochondrial axis, and consequently enhanced the osteoinductivity of BMP-2. Based on the mechanistic discovery, microgel composite hydrogels were fabricated as low-dose BMP-2/Mg2+ codelivery system through microfluidic and 3D printing technologies. An in vivo study further confirmed that rapid and robust bone regeneration was induced by the codelivery system. Collectively, these results suggest that this bioenergetic-driven, cost-effective, low-dose BMP-2-based strategy has substantial potential for bone repair.http://www.sciencedirect.com/science/article/pii/S2452199X22001396BiomaterialsBone morphogenetic protein-2MagnesiumEnergy metabolismBone regeneration |
| spellingShingle | Sihan Lin Shi Yin Junfeng Shi Guangzheng Yang Xutao Wen Wenjie Zhang Mingliang Zhou Xinquan Jiang Orchestration of energy metabolism and osteogenesis by Mg2+ facilitates low-dose BMP-2-driven regeneration Bioactive Materials Biomaterials Bone morphogenetic protein-2 Magnesium Energy metabolism Bone regeneration |
| title | Orchestration of energy metabolism and osteogenesis by Mg2+ facilitates low-dose BMP-2-driven regeneration |
| title_full | Orchestration of energy metabolism and osteogenesis by Mg2+ facilitates low-dose BMP-2-driven regeneration |
| title_fullStr | Orchestration of energy metabolism and osteogenesis by Mg2+ facilitates low-dose BMP-2-driven regeneration |
| title_full_unstemmed | Orchestration of energy metabolism and osteogenesis by Mg2+ facilitates low-dose BMP-2-driven regeneration |
| title_short | Orchestration of energy metabolism and osteogenesis by Mg2+ facilitates low-dose BMP-2-driven regeneration |
| title_sort | orchestration of energy metabolism and osteogenesis by mg2 facilitates low dose bmp 2 driven regeneration |
| topic | Biomaterials Bone morphogenetic protein-2 Magnesium Energy metabolism Bone regeneration |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X22001396 |
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