Physical and chemical niche of human growth plate for polarized bone development
Abstract Growth plate (GP), a critical cartilaginous structure in amniotes, underpins longitudinal bone growth, yet the intricate mechanisms behind its polarized mineralization during evolution remain unclear. Herein, employing high-resolution analytical techniques, we reveal that the GP-epiphysis i...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-08-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-62711-z |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849764257689763840 |
|---|---|
| author | Chang Xie Wenyue Li Xudong Yao Boxuan Wu Jinghua Fang Renwei Mao Yiyang Yan Hongxu Meng Yan Wu Xianzhu Zhang Rui Li Jie Zhang Wangping Duan Xuesong Dai Xiaozhao Wang Hongwei Ouyang |
| author_facet | Chang Xie Wenyue Li Xudong Yao Boxuan Wu Jinghua Fang Renwei Mao Yiyang Yan Hongxu Meng Yan Wu Xianzhu Zhang Rui Li Jie Zhang Wangping Duan Xuesong Dai Xiaozhao Wang Hongwei Ouyang |
| author_sort | Chang Xie |
| collection | DOAJ |
| description | Abstract Growth plate (GP), a critical cartilaginous structure in amniotes, underpins longitudinal bone growth, yet the intricate mechanisms behind its polarized mineralization during evolution remain unclear. Herein, employing high-resolution analytical techniques, we reveal that the GP-epiphysis interface displays a sharp transition in tissue modulus, acting as a protective shell for the underlying GP, whereas the GP-metaphysis interface exhibits a gradual modulus increase, enabling efficient load redistribution to the metaphysis. This mechanical microenvironment contributes to unique microstructural and compositional transformations from GP to epiphysis and metaphysis. Notably, the GP-epiphysis interface acts as a mineralization inhibition zone while the GP-metaphysis serves as a mineralization promotion zone, orchestrated by a complex network of proteins. Proteins such as secreted phosphoprotein 1 (SPP1) and alpha-2-HS-glycoprotein (AHSG) at the GP-epiphysis interface inhibit mineralization, forming a defense line; while ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) and alkaline phosphatase, biomineralization associated (ALPL), coexisting with SPP1 and AHSG, promote a sequential nucleation and assembly of calcium phosphate minerals at the GP-metaphysis. Such polarized mineralization patterns maintain the homeostasis of GPs and drive polarized bone elongation. Replicating this process in vitro, we synthesize stable amorphous calcium phosphate which shows highly controlled transformation into hydroxyapatite. This work provides a more comprehensive view of the structural integrity of human bone in development and offers strategies for controlled biomineralization. |
| format | Article |
| id | doaj-art-baae47e9dbe24ea5bb02b6ea1bc18895 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-baae47e9dbe24ea5bb02b6ea1bc188952025-08-20T03:05:10ZengNature PortfolioNature Communications2041-17232025-08-0116111510.1038/s41467-025-62711-zPhysical and chemical niche of human growth plate for polarized bone developmentChang Xie0Wenyue Li1Xudong Yao2Boxuan Wu3Jinghua Fang4Renwei Mao5Yiyang Yan6Hongxu Meng7Yan Wu8Xianzhu Zhang9Rui Li10Jie Zhang11Wangping Duan12Xuesong Dai13Xiaozhao Wang14Hongwei Ouyang15Department of Sports Medicine of the Second Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of MedicineDepartment of Sports Medicine of the Second Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of MedicineCenter of Regenerative and Aging Medicine, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang UniversityDepartment of Sports Medicine of the Second Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of MedicineDepartment of Sports Medicine of the Second Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of MedicineDepartment of Biomedical Engineering, The Hong Kong Polytechnic UniversityDepartment of Sports Medicine of the Second Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of MedicineDepartment of Sports Medicine of the Second Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of MedicineDepartment of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang UniversityDepartment of Sports Medicine of the Second Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of MedicineDepartment of Sports Medicine of the Second Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of MedicineDepartment of Sports Medicine of the Second Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of MedicineDepartment of Orthopedics, Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair, Second Hospital of Shanxi Medical UniversityDepartment of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang UniversityDepartment of Sports Medicine of the Second Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of MedicineDepartment of Sports Medicine of the Second Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of MedicineAbstract Growth plate (GP), a critical cartilaginous structure in amniotes, underpins longitudinal bone growth, yet the intricate mechanisms behind its polarized mineralization during evolution remain unclear. Herein, employing high-resolution analytical techniques, we reveal that the GP-epiphysis interface displays a sharp transition in tissue modulus, acting as a protective shell for the underlying GP, whereas the GP-metaphysis interface exhibits a gradual modulus increase, enabling efficient load redistribution to the metaphysis. This mechanical microenvironment contributes to unique microstructural and compositional transformations from GP to epiphysis and metaphysis. Notably, the GP-epiphysis interface acts as a mineralization inhibition zone while the GP-metaphysis serves as a mineralization promotion zone, orchestrated by a complex network of proteins. Proteins such as secreted phosphoprotein 1 (SPP1) and alpha-2-HS-glycoprotein (AHSG) at the GP-epiphysis interface inhibit mineralization, forming a defense line; while ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) and alkaline phosphatase, biomineralization associated (ALPL), coexisting with SPP1 and AHSG, promote a sequential nucleation and assembly of calcium phosphate minerals at the GP-metaphysis. Such polarized mineralization patterns maintain the homeostasis of GPs and drive polarized bone elongation. Replicating this process in vitro, we synthesize stable amorphous calcium phosphate which shows highly controlled transformation into hydroxyapatite. This work provides a more comprehensive view of the structural integrity of human bone in development and offers strategies for controlled biomineralization.https://doi.org/10.1038/s41467-025-62711-z |
| spellingShingle | Chang Xie Wenyue Li Xudong Yao Boxuan Wu Jinghua Fang Renwei Mao Yiyang Yan Hongxu Meng Yan Wu Xianzhu Zhang Rui Li Jie Zhang Wangping Duan Xuesong Dai Xiaozhao Wang Hongwei Ouyang Physical and chemical niche of human growth plate for polarized bone development Nature Communications |
| title | Physical and chemical niche of human growth plate for polarized bone development |
| title_full | Physical and chemical niche of human growth plate for polarized bone development |
| title_fullStr | Physical and chemical niche of human growth plate for polarized bone development |
| title_full_unstemmed | Physical and chemical niche of human growth plate for polarized bone development |
| title_short | Physical and chemical niche of human growth plate for polarized bone development |
| title_sort | physical and chemical niche of human growth plate for polarized bone development |
| url | https://doi.org/10.1038/s41467-025-62711-z |
| work_keys_str_mv | AT changxie physicalandchemicalnicheofhumangrowthplateforpolarizedbonedevelopment AT wenyueli physicalandchemicalnicheofhumangrowthplateforpolarizedbonedevelopment AT xudongyao physicalandchemicalnicheofhumangrowthplateforpolarizedbonedevelopment AT boxuanwu physicalandchemicalnicheofhumangrowthplateforpolarizedbonedevelopment AT jinghuafang physicalandchemicalnicheofhumangrowthplateforpolarizedbonedevelopment AT renweimao physicalandchemicalnicheofhumangrowthplateforpolarizedbonedevelopment AT yiyangyan physicalandchemicalnicheofhumangrowthplateforpolarizedbonedevelopment AT hongxumeng physicalandchemicalnicheofhumangrowthplateforpolarizedbonedevelopment AT yanwu physicalandchemicalnicheofhumangrowthplateforpolarizedbonedevelopment AT xianzhuzhang physicalandchemicalnicheofhumangrowthplateforpolarizedbonedevelopment AT ruili physicalandchemicalnicheofhumangrowthplateforpolarizedbonedevelopment AT jiezhang physicalandchemicalnicheofhumangrowthplateforpolarizedbonedevelopment AT wangpingduan physicalandchemicalnicheofhumangrowthplateforpolarizedbonedevelopment AT xuesongdai physicalandchemicalnicheofhumangrowthplateforpolarizedbonedevelopment AT xiaozhaowang physicalandchemicalnicheofhumangrowthplateforpolarizedbonedevelopment AT hongweiouyang physicalandchemicalnicheofhumangrowthplateforpolarizedbonedevelopment |