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Wei X, Lei L, Luo L, Zhou Y, Zheng Z, Chen W. Advances in osteoimmunomodulation of biomaterials after intrabone implantation: focus on surface hydrophilicity. J Mater Chem B 2024; 12:11089-11104. [PMID: 39387541 DOI: 10.1039/d4tb01907e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/15/2024]
Abstract
Biomaterials intended for intrabone implantation are extensively utilized in orthopedic and dental applications. Their surface properties, particularly hydrophilicity, significantly influence the biological interactions surrounding the implant, ultimately determining the implant's in vivo fate. Recently, the role of osteoimmunomodulation in these implantable biomaterials has been recognized for its importance in regulating biomaterial-mediated osteogenesis. Consequently, it is imperative to elucidate the correlation between hydrophilicity and the immune response for the development of osteoimmunomodulatory implants. Herein, this review highlights recent advances in osteoimmunomodulation of biomaterials after intrabone implantation from a novel perspective-surface hydrophilicity, and summarizes the series of immune reactions and subsequent bone remodeling that occur in response to hydrophilic implants, focusing on protein adsorption, the behaviors of major immune cells, and osteoimmunomodulation-enhanced angiogenesis and osteogenesis. Hydrophilic biomaterials have the capacity to alter the surrounding immune microenvironment and accelerate the process of material-tissue bonding, thereby facilitating the successful integration of biomaterials with tissue. Collectively, the authors hope that this article provides strategies for modulating hydrophilicity to achieve osteoimmunomodulatory performance and further promotes the development of novel implantable biomaterials for orthopedic and dental applications.
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Affiliation(s)
- Xinpeng Wei
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
| | - Linshan Lei
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
| | - Ling Luo
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China.
| | - Ying Zhou
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China.
| | - Zheng Zheng
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China.
| | - Wenchuan Chen
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China.
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Pandit A, Indurkar A, Locs J, Haugen HJ, Loca D. Calcium Phosphates: A Key to Next-Generation In Vitro Bone Modeling. Adv Healthc Mater 2024; 13:e2401307. [PMID: 39175382 PMCID: PMC11582516 DOI: 10.1002/adhm.202401307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Revised: 08/06/2024] [Indexed: 08/24/2024]
Abstract
The replication of bone physiology under laboratory conditions is a prime target behind the development of in vitro bone models. The model should be robust enough to elicit an unbiased response when stimulated experimentally, giving reproducible outcomes. In vitro bone tissue generation majorly requires the availability of cellular components, the presence of factors promoting cellular proliferation and differentiation, efficient nutrient supply, and a supporting matrix for the cells to anchor - gaining predefined topology. Calcium phosphates (CaP) are difficult to ignore while considering the above requirements of a bone model. Therefore, the current review focuses on the role of CaP in developing an in vitro bone model addressing the prerequisites of bone tissue generation. Special emphasis is given to the physico-chemical properties of CaP that promote osteogenesis, angiogenesis and provide sufficient mechanical strength for load-bearing applications. Finally, the future course of action is discussed to ensure efficient utilization of CaP in the in vitro bone model development field.
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Affiliation(s)
- Ashish Pandit
- Institute of Biomaterials and BioengineeringFaculty of Natural Sciences and TechnologyRiga Technical UniversityPulka Street 3RigaLV‐1007Latvia
- Baltic Biomaterials Centre of ExcellenceHeadquarters at Riga Technical UniversityRigaLV‐1007Latvia
| | - Abhishek Indurkar
- Institute of Biomaterials and BioengineeringFaculty of Natural Sciences and TechnologyRiga Technical UniversityPulka Street 3RigaLV‐1007Latvia
- Baltic Biomaterials Centre of ExcellenceHeadquarters at Riga Technical UniversityRigaLV‐1007Latvia
| | - Janis Locs
- Institute of Biomaterials and BioengineeringFaculty of Natural Sciences and TechnologyRiga Technical UniversityPulka Street 3RigaLV‐1007Latvia
- Baltic Biomaterials Centre of ExcellenceHeadquarters at Riga Technical UniversityRigaLV‐1007Latvia
| | | | - Dagnija Loca
- Institute of Biomaterials and BioengineeringFaculty of Natural Sciences and TechnologyRiga Technical UniversityPulka Street 3RigaLV‐1007Latvia
- Baltic Biomaterials Centre of ExcellenceHeadquarters at Riga Technical UniversityRigaLV‐1007Latvia
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Lu Y, Ma C, Zhang Y, Zhu W, Huangfu S, Zhou Y, Zhou C, Qin F, Wang J, Li M, Jiang B. The impact and mechanism study of Sijunzi decoction and Rg1 on proliferation and differentiation of human umbilical cord mesenchymal stem cells: An experimental study. Medicine (Baltimore) 2024; 103:e39350. [PMID: 39151516 PMCID: PMC11332729 DOI: 10.1097/md.0000000000039350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 05/06/2024] [Accepted: 07/26/2024] [Indexed: 08/19/2024] Open
Abstract
BACKGROUND Previous researches have demonstrated that the traditional Chinese medicine could therapeutically treat inflammatory and hypoxic diseases by enhancing the functionality of mesenchymal stem cells. However, its mechanism was not yet clear. This research aimed to investigate the impact of the traditional Chinese medicine Sijunzi decoction and its herb monomer ginsenoside Rg1 on the proliferation and differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs) and explore the underlying mechanisms. METHODS Different concentrations of Sijunzi decoction and Rg1 were applied to differentiating induced hUC-MSCs. The CCK-8 test was utilized to evaluate cell proliferation activity and identify suitable drug concentrations. Alizarin Red staining was employed to detect the formation of calcium nodules, and Oil Red O staining was used to assess the formation of lipid droplets. PCR was utilized to examine gene expression related to osteogenic differentiation, adipogenic differentiation, and the HIF-1α signaling pathway in hUC-MSCs. Western blot analysis was conducted to evaluate protein expression in osteogenic differentiation and HIF-1α. ELISA was performed to measure HIF-1α signaling factors and inflammatory cytokine expression. Biochemical assays were used to assess changes in oxidative stress indicators. RESULTS The Sijunzi decoction and Rg1 both demonstrated a dose-dependent promotion of hUC-MSC proliferation. The Sijunzi decoction significantly increased the expression of genes and proteins relevant to osteogenesis, such as osterix, osteocalcin, RUNX2, and osteopontin, and activated the HIF-1α pathway in hUC-MSCs. (P < .05). Similar effects were observed at the gene level after treatment with Rg1. Simultaneously, Sijunzi decoction significantly reduced the secretion of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β, while increasing the secretion of the anti-inflammatory cytokine IL-10 during osteogenic differentiation (P < .05). Moreover, Sijunzi decoction lowered oxidative stress levels and enhanced the antioxidant capacity of hUC-MSCs during osteogenic differentiation (P < .05). However, the impact of Sijunzi decoction on hUC-MSCs toward adipogenic differentiation was not significant (P > .05). CONCLUSION Sijunzi decoction promotes the proliferation and osteogenic differentiation of hUC-MSCs, potentially through the activation of the HIF-1α signaling pathway and by modulating the microenvironment via reducing inflammation and oxidative stress levels. Rg1 might be involved in this process.
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Affiliation(s)
- Yafei Lu
- National Colorectal Disease Center, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, PR China
| | - Chuanxue Ma
- National Colorectal Disease Center, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, PR China
| | - Yajie Zhang
- Central Laboratory, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, PR China
- Department of Biobank, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, PR China
| | - Weina Zhu
- Central Laboratory, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, PR China
- Department of Biobank, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, PR China
| | - Shaohua Huangfu
- National Colorectal Disease Center, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, PR China
| | - Ying Zhou
- National Colorectal Disease Center, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, PR China
| | - Chungen Zhou
- National Colorectal Disease Center, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, PR China
| | - Fuhao Qin
- National Colorectal Disease Center, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, PR China
| | - Jianmin Wang
- Colorectal Disease Center, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, PR China
| | - Ming Li
- Colorectal Disease Center, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, PR China
| | - Bin Jiang
- National Colorectal Disease Center, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, PR China
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Guo F, Li J, Chen Z, Wang T, Wang R, Wang T, Bian Y, Du Y, Yuan H, Pan Y, Jin J, Jiang H, Han F, Jiang J, Wu F, Wang Y. An Injectable Black Phosphorus Hydrogel for Rapid Tooth Extraction Socket Healing. ACS APPLIED MATERIALS & INTERFACES 2024; 16:25799-25812. [PMID: 38727024 DOI: 10.1021/acsami.4c03278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/24/2024]
Abstract
The excess production of reactive oxygen species (ROS) will delay tooth extraction socket (TES) healing. In this study, we developed an injectable thermosensitive hydrogel (NBP@BP@CS) used to treat TES healing. The hydrogel formulation incorporated black phosphorus (BP) nanoflakes, recognized for their accelerated alveolar bone regeneration and ROS-scavenging properties, and dl-3-n-butylphthalide (NBP), a vasodilator aimed at enhancing angiogenesis. In vivo investigations strongly demonstrated that NBP@BP@CS improved TES healing due to antioxidation and promotion of alveolar bone regeneration by BP nanoflakes. The sustained release of NBP from the hydrogel promoted neovascularization and vascular remodeling. Our results demonstrated that the designed thermosensitive hydrogel provided great opportunity not only for ROS elimination but also for the promotion of osteogenesis and angiogenesis, reflecting the "three birds with one stone" concept, and has tremendous potential for rapid TES healing.
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Affiliation(s)
- Fanyi Guo
- Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital of Nanjing Medical University, Jiangsu Province Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Centre of Stomatological Translational Medicine, Nanjing Medical University, Nanjing 210029, Jiangsu, China
| | - Jianfeng Li
- Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital of Nanjing Medical University, Jiangsu Province Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Centre of Stomatological Translational Medicine, Nanjing Medical University, Nanjing 210029, Jiangsu, China
| | - Ziyu Chen
- Medical Basic Research Innovation Center for Cardiovascular and Cerebrovascular Diseases, Ministry of Education, International Joint Laboratory for Drug Target of Critical Illnesses, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Tianxiao Wang
- Medical Basic Research Innovation Center for Cardiovascular and Cerebrovascular Diseases, Ministry of Education, International Joint Laboratory for Drug Target of Critical Illnesses, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Ruyu Wang
- Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital of Nanjing Medical University, Jiangsu Province Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Centre of Stomatological Translational Medicine, Nanjing Medical University, Nanjing 210029, Jiangsu, China
| | - Tianyao Wang
- Department of Periodontology, The Affiliated Stomatological Hospital of Nanjing Medical University, Jiangsu Province Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Centre of Stomatological Translational Medicine, Nanjing Medical University, Nanjing 210029, Jiangsu, China
| | - Yifeng Bian
- Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital of Nanjing Medical University, Jiangsu Province Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Centre of Stomatological Translational Medicine, Nanjing Medical University, Nanjing 210029, Jiangsu, China
| | - Yifei Du
- Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital of Nanjing Medical University, Jiangsu Province Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Centre of Stomatological Translational Medicine, Nanjing Medical University, Nanjing 210029, Jiangsu, China
| | - Hua Yuan
- Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital of Nanjing Medical University, Jiangsu Province Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Centre of Stomatological Translational Medicine, Nanjing Medical University, Nanjing 210029, Jiangsu, China
| | - Yongchu Pan
- Department of Orthodontic, The Affiliated Stomatological Hospital of Nanjing Medical University, Jiangsu Province Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Centre of Stomatological Translational Medicine, Nanjing Medical University, Nanjing 210029, Jiangsu, China
| | - Jianliang Jin
- Department of Human Anatomy, Research Centre for Bone and Stem Cells, School of Basic Medical Sciences, Key Laboratory for Aging & Disease, School of Biomedical Engineering and informatics, Nanjing Medical University, Nanjing 211166, Jiangsu, China
| | - Huijun Jiang
- Medical Basic Research Innovation Center for Cardiovascular and Cerebrovascular Diseases, Ministry of Education, International Joint Laboratory for Drug Target of Critical Illnesses, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Feng Han
- Medical Basic Research Innovation Center for Cardiovascular and Cerebrovascular Diseases, Ministry of Education, International Joint Laboratory for Drug Target of Critical Illnesses, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Jiandong Jiang
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
| | - Fan Wu
- Medical Basic Research Innovation Center for Cardiovascular and Cerebrovascular Diseases, Ministry of Education, International Joint Laboratory for Drug Target of Critical Illnesses, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Yuli Wang
- Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital of Nanjing Medical University, Jiangsu Province Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Centre of Stomatological Translational Medicine, Nanjing Medical University, Nanjing 210029, Jiangsu, China
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Li YB, Zhang HQ, Lu YP, Yang XJ, Wang GD, Wang YY, Tang KL, Huang SY, Xiao GY. Construction of Magnesium Phosphate Chemical Conversion Coatings with Different Microstructures on Titanium to Enhance Osteogenesis and Angiogenesis. ACS APPLIED MATERIALS & INTERFACES 2024; 16:21672-21688. [PMID: 38637290 DOI: 10.1021/acsami.4c03024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/20/2024]
Abstract
Titanium (Ti) and its alloys are widely used as hard tissue substitutes in dentistry and orthopedics, but their low bioactivity leads to undesirable osseointegration defects in the early osteogenic phase. Surface modification is an important approach to overcome these problems. In the present study, novel magnesium phosphate (MgP) coatings with controllable structures were fabricated on the surface of Ti using the phosphate chemical conversion (PCC) method. The effects of the microstructure on the physicochemical and biological properties of the coatings on Ti were researched. The results indicated that accelerators in PCC solution were important factors affecting the microstructure and properties of the MgP coatings. In addition, the coated Ti exhibited excellent hydrophilicity, high bonding strength, and good corrosion resistance. Moreover, the biological results showed that the MgP coatings could improve the spread, proliferation, and osteogenic differentiation of mouse osteoblast cells (MC3T3-E1) and vascular differentiation of human umbilical vein endothelial cells (HUVECs), indicating that the coated Ti samples had a great effect on promoting osteogenesis and angiogenesis. Overall, this study provided a new research idea for the surface modification of conventional Ti to enhance osteogenesis and angiogenesis in different bone types for potential biomedical applications.
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Affiliation(s)
- Yi-Bo Li
- Key Laboratory for Liquid-Solid Structural Evolution and Processing of Materials, Ministry of Education, Shandong University, Jinan 250061, China
- School of Materials Science and Engineering, Shandong University, Jinan 250061, China
| | - Huan-Qing Zhang
- Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital, Shandong University, Jinan 250021, China
| | - Yu-Peng Lu
- Key Laboratory for Liquid-Solid Structural Evolution and Processing of Materials, Ministry of Education, Shandong University, Jinan 250061, China
- School of Materials Science and Engineering, Shandong University, Jinan 250061, China
| | - Xiao-Juan Yang
- Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital, Shandong University, Jinan 250021, China
| | - Guan-Duo Wang
- Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital, Shandong University, Jinan 250021, China
| | - Yu-Ying Wang
- Key Laboratory for Liquid-Solid Structural Evolution and Processing of Materials, Ministry of Education, Shandong University, Jinan 250061, China
- School of Materials Science and Engineering, Shandong University, Jinan 250061, China
| | - Kang-le Tang
- Key Laboratory for Liquid-Solid Structural Evolution and Processing of Materials, Ministry of Education, Shandong University, Jinan 250061, China
- School of Materials Science and Engineering, Shandong University, Jinan 250061, China
| | - Sheng-Yun Huang
- Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital, Shandong University, Jinan 250021, China
- Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China
| | - Gui-Yong Xiao
- Key Laboratory for Liquid-Solid Structural Evolution and Processing of Materials, Ministry of Education, Shandong University, Jinan 250061, China
- School of Materials Science and Engineering, Shandong University, Jinan 250061, China
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Zhang Y, Dai J, Hang R, Yao X, Bai L, Huang D, Hang R. Impact of surface biofunctionalization strategies on key effector cells response in polyacrylamide hydrogels for bone regeneration. BIOMATERIALS ADVANCES 2024; 158:213768. [PMID: 38237320 DOI: 10.1016/j.bioadv.2024.213768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Revised: 12/24/2023] [Accepted: 01/10/2024] [Indexed: 03/03/2024]
Abstract
Despite the clinical prevalence of various bone defect repair materials, a full understanding of their influence on bone repair and regeneration remains elusive. This study focuses on poly(acrylamide) (PAAm) hydrogels, popular 2D model substrates, which have regulable mechanical properties within physiological. However, their bio-inert nature requires surface biofunctionalization to enhance cell-material interactions and facilitate the study of bone repair mechanisms. We utilized PAAm hydrogels of varying stiffness (18, 76 and 295 kPa), employed sulfosuccinimidyl-6-(4'-azido-2'-nitropheny-lamino) hexanoate (sulfo-SANPAH) and N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride/N-hydroxysuccinimidyl acrylate (EDC/NHS) as crosslinkers, and cultured macrophages, endothelial cells, and bone mesenchymal stem cells on these hydrogels. Our findings indicated that sulfo-SANPAH's crosslinking efficiency surpassed that of EDC/NHS, irrespective of pore size and stiffness. Importantly, we observed that the stiffness and surface biofunctionalization method of hydrogels significantly impacted cell adhesion and proliferation. The collagen-modified hydrogels by EDC/NHS strategy failed to support the normal biological behavior of bone mesenchymal stem cells and hindered endothelial cell spreading. In contrast, these modified hydrogels by the sulfo-SANPAH method showed good cytocompatibility with the three types of cells. This study underscores the critical role of appropriate conjugation strategies for PAAm hydrogels, providing valuable insights for hydrogel surface modification in bone repair and regeneration research.
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Affiliation(s)
- Yi Zhang
- Shanxi Key Laboratory of Biomedical Metal Materials, College of Materials Science and Engineering, Taiyuan University of Technology, Taiyuan 030024, China
| | - Jinjun Dai
- Shanxi Key Laboratory of Biomedical Metal Materials, College of Materials Science and Engineering, Taiyuan University of Technology, Taiyuan 030024, China
| | - Ruiyue Hang
- Shanxi Key Laboratory of Biomedical Metal Materials, College of Materials Science and Engineering, Taiyuan University of Technology, Taiyuan 030024, China
| | - Xiaohong Yao
- Shanxi Key Laboratory of Biomedical Metal Materials, College of Materials Science and Engineering, Taiyuan University of Technology, Taiyuan 030024, China.
| | - Long Bai
- Institute of Translational Medicine, Shanghai University, Shanghai 200444, China.
| | - Di Huang
- Research Center for Nano-Biomaterials & Regenerative Medicine, Department of Biomedical Engineering, College of Biomedical Engineering, Taiyuan University of Technology, Taiyuan 030024, China; Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering, Taiyuan 030060, China
| | - Ruiqiang Hang
- Shanxi Key Laboratory of Biomedical Metal Materials, College of Materials Science and Engineering, Taiyuan University of Technology, Taiyuan 030024, China.
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Jin L, Long Y, Zhang Q, Long J. MiRNAs regulate cell communication in osteogenesis-angiogenesis coupling during bone regeneration. Mol Biol Rep 2023; 50:8715-8728. [PMID: 37642761 DOI: 10.1007/s11033-023-08709-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Accepted: 07/25/2023] [Indexed: 08/31/2023]
Abstract
Bone regeneration is a complex process that requires not only the participation of multiple cell types, but also signal communication between cells. The two basic processes of osteogenesis and angiogenesis are closely related to bone regeneration and bone homeostasis. H-type vessels are a subtype of bone vessels characterized by high expression of CD31 and EMCN. These vessels play a key role in the regulation of bone regeneration and are important mediators of coupling between osteogenesis and angiogenesis. Molecular regulation between different cell types is important for coordination of osteogenesis and angiogenesis that promotes bone regeneration. MiRNAs are small non-coding RNAs that predominantly regulate gene expression at the post-transcriptional level and are closely related to cell communication. Specifically, miRNAs transduce external stimuli through various cell signaling pathways and cause a series of physiological and pathological effects. They are also deeply involved in the bone repair process. This review focuses on three signaling pathways related to osteogenesis-angiogenesis coupling, as well as the miRNAs involved in these pathways. Elucidation of the molecular mechanisms governing osteogenesis and angiogenesis is of great significance for bone regeneration.
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Affiliation(s)
- Liangyu Jin
- The State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, 610041, PR China
- Department of Oral and Maxillofacial Surgery, West China College of Stomatology, Sichuan University, Chengdu, 610041, PR China
- National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, 610041, PR China
| | - Yifei Long
- The State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, 610041, PR China
- National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, 610041, PR China
| | - Qiuling Zhang
- The State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, 610041, PR China
- Department of Oral and Maxillofacial Surgery, West China College of Stomatology, Sichuan University, Chengdu, 610041, PR China
- National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, 610041, PR China
| | - Jie Long
- The State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, 610041, PR China.
- Department of Oral and Maxillofacial Surgery, West China College of Stomatology, Sichuan University, Chengdu, 610041, PR China.
- National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, 610041, PR China.
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Hu Y, Li H. Deferoxamine mesylate enhances mandibular advancement-induced condylar osteogenesis by promoting H-type angiogenesis. J Oral Rehabil 2023; 50:234-242. [PMID: 36588468 DOI: 10.1111/joor.13410] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 12/14/2022] [Accepted: 12/29/2022] [Indexed: 01/03/2023]
Abstract
BACKGROUND The effect of functional orthopaedic treatment for mandibular deficiency relies on mandibular advancement (MA)-induced condylar new bone formation. However, this is not easy to achieve, especially in non-growing patients. Therefore, how to obtain reliable MA-induced condylar osteogenesis is a subject much worthy of study. OBJECTIVE To investigate whether deferoxamine mesylate (DFM) enhances MA-induced condylar osteogenesis in middle-aged mice. METHODS Forty 30-week-old male C57BL/6J mice were randomly divided into 4 groups: the control (Ctrl), DFM, MA + Ctrl and MA + DFM groups. After a 4-week experimental period, femurs, tibias and condyles were collected for morphological, micro-computed tomography and histological evaluation. RESULTS For long bones, DFM reversed osteoporosis in middle-aged mice by promoting H-type angiogenesis. For mandibular condyles, MA promoted condylar osteogenesis in middle-aged mice, thereby allowing the mandible to achieve a stable protruding position. In addition, DFM enhanced the volume and quality of MA-induced condylar new bone formation. Furthermore, histological analysis revealed that DFM enhanced MA-induced condylar subchondral ossification. Mechanistically, it was confirmed that DFM increased the number of H-type vessels and their coupled Osterix+ osteoprogenitors by upregulating the hypoxia-inducible factor (HIF)-1α signalling pathway, thereby enhancing MA-induced condylar osteogenesis. CONCLUSION Applying DFM to enhance MA-induced condylar osteogenesis through H-type angiogenesis is expected to be an effective strategy to achieve favourable functional orthopaedic treatment effectiveness in non-growing patients.
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Affiliation(s)
- Yun Hu
- Department of Orthodontics, Stomatological Hospital, Southern Medical University, Guangzhou, China
| | - Hegang Li
- Department of Orthodontics, Stomatological Hospital, Southern Medical University, Guangzhou, China
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9
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Shao H, Ma M, Wang Q, Yan T, Zhao B, Guo S, Tong S. Advances in the superhydrophilicity-modified titanium surfaces with antibacterial and pro-osteogenesis properties: A review. Front Bioeng Biotechnol 2022; 10:1000401. [PMID: 36147527 PMCID: PMC9485881 DOI: 10.3389/fbioe.2022.1000401] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Accepted: 08/17/2022] [Indexed: 12/12/2022] Open
Abstract
In recent years, the rate of implant failure has been increasing. Microbial infection was the primary cause, and the main stages included bacterial adhesion, biofilm formation, and severe inhibition of implant osseointegration. Various biomaterials and their preparation methods have emerged to produce specific implants with antimicrobial or bactericidal properties to reduce implant infection caused by bacterial adhesion and effectively promote bone and implant integration. In this study, we reviewed the research progress of bone integration promotion and antibacterial action of superhydrophilic surfaces based on titanium alloys. First, the adverse reactions caused by bacterial adhesion to the implant surface, including infection and bone integration deficiency, are briefly introduced. Several commonly used antibacterial methods of titanium alloys are introduced. Secondly, we discuss the antibacterial properties of superhydrophilic surfaces based on ultraviolet photo-functionalization and plasma treatment, in contrast to the antibacterial principle of superhydrophobic surface morphology. Thirdly, the osteogenic effects of superhydrophilic surfaces are described, according to the processes of osseointegration: osteogenic immunity, angiogenesis, and osteogenic related cells. Finally, we discuss the challenges and prospects for the development of this superhydrophilic surface in clinical applications, as well as the prominent strategies and directions for future research.
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Affiliation(s)
- Hanyu Shao
- Department of Plastic Surgery, First Hospital of China Medical University, Shenyang, China
| | - Mingchen Ma
- School and Hospital of Stomatology, China Medical University, Shenyang, China
| | - Qiang Wang
- School and Hospital of Stomatology, China Medical University, Shenyang, China
| | - Tingting Yan
- Faculty of Materials Science and Engineering, Kunming University of Science and Technology, Kunming, China
| | - Baohong Zhao
- School and Hospital of Stomatology, China Medical University, Shenyang, China
| | - Shu Guo
- Department of Plastic Surgery, First Hospital of China Medical University, Shenyang, China
| | - Shuang Tong
- Department of Plastic Surgery, First Hospital of China Medical University, Shenyang, China
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10
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Zhao Y, Sun Y, Hang R, Yao R, Zhang Y, Huang D, Yao X, Bai L, Hang R. Biocompatible silane adhesion layer on titanium implants improves angiogenesis and osteogenesis. BIOMATERIALS ADVANCES 2022; 139:213033. [PMID: 35882124 DOI: 10.1016/j.bioadv.2022.213033] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 07/02/2022] [Accepted: 07/12/2022] [Indexed: 06/15/2023]
Abstract
Silane adhesion layer strategy has been widely used to covalently graft biomolecules to the titanium implant surface, thereby conferring the implant bioactivity to ameliorate osseointegration. However, few researchers pay attention to the effects of silanization parameters on biocompatibility and biofunctionality of the silane adhesion layers. Accordingly, the present study successfully fabricated the silane adhesion layers with different thickness, intactness, and surface morphologies by introducing 3-aminopropyltriethoxysilane on the alkali-treated titanium surface in time-varied processing of silanization. The regulatory effects of the silane adhesion layers on angiogenesis and osteogenesis were assessed in vitro. Results showed that the prolonged silanization processing time increased the thickness and intactness of the silane adhesion layer and significantly improved its biocompatibility. Notably, the silane adhesion layer prepared after 12 h of silanization exhibited a brain-like surface morphology and benefited the adhesion and proliferation of endothelial cells (ECs) and osteoblasts (OBs). Moreover, the layer promoted angiogenesis via stimulating vascular endothelial growth factor (VEGF) secretion and nitric oxide (NO) production of ECs. Simultaneously, it improved osteogenesis by enhancing alkaline phosphatase (ALP) activity, collagen secretion, and extracellular matrix mineralization of OBs. This work systematically investigated the biocompatibility and biofunctionality of the modified silane adhesion layers, thus providing valuable references for their application in covalently grafting biomolecules on the titanium implant surface.
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Affiliation(s)
- Yuyu Zhao
- Shanxi Key Laboratory of Biomedical Metal Materials, College of Materials Science and Engineering, Taiyuan University of Technology, Taiyuan 030024, China
| | - Yonghua Sun
- Shanxi Key Laboratory of Biomedical Metal Materials, College of Materials Science and Engineering, Taiyuan University of Technology, Taiyuan 030024, China
| | - Ruiyue Hang
- Shanxi Key Laboratory of Biomedical Metal Materials, College of Materials Science and Engineering, Taiyuan University of Technology, Taiyuan 030024, China
| | - Runhua Yao
- Shanxi Key Laboratory of Biomedical Metal Materials, College of Materials Science and Engineering, Taiyuan University of Technology, Taiyuan 030024, China
| | - Yi Zhang
- Shanxi Key Laboratory of Biomedical Metal Materials, College of Materials Science and Engineering, Taiyuan University of Technology, Taiyuan 030024, China
| | - Di Huang
- Department of Biomedical Engineering, Research Center for Nano-biomaterials & Regenerative Medicine, College of Biomedical Engineering, Taiyuan University of Technology, Taiyuan 030024, China; Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering, Taiyuan 030032, China
| | - Xiaohong Yao
- Shanxi Key Laboratory of Biomedical Metal Materials, College of Materials Science and Engineering, Taiyuan University of Technology, Taiyuan 030024, China.
| | - Long Bai
- Institute of Translational Medicine, Shanghai University, Shanghai, 200444 China; Engineering Research Center for Biomedical Materials of Ministry of Education, College of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
| | - Ruiqiang Hang
- Shanxi Key Laboratory of Biomedical Metal Materials, College of Materials Science and Engineering, Taiyuan University of Technology, Taiyuan 030024, China.
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11
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Cui Y, Li Z, Guo Y, Qi X, Yang Y, Jia X, Li R, Shi J, Gao W, Ren Z, Liu G, Ye Q, Zhang Z, Fu D. Bioinspired Nanovesicles Convert the Skeletal Endothelium-Associated Secretory Phenotype to Treat Osteoporosis. ACS NANO 2022; 16:11076-11091. [PMID: 35801837 DOI: 10.1021/acsnano.2c03781] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Recently, bone marrow endothelial cells (BMECs) were found to play an important role in regulating bone homeostasis. However, few studies utilized BMECs to treat bone metabolic diseases including osteoporosis. Here, we reported bioinspired nanovesicles (BNVs) prepared from human induced pluripotent stem cells-derived endothelial cells under hypoxia culture through an extrusion approach. Abundant membrane C-X-C motif chemokine receptor 4 conferred these BNVs bone-targeting ability and the endothelial homology facilitated the BMEC tropism. Due to their unique endogenous miRNA cargos, these BNVs re-educated BMECs to secret cytokines favoring osteogenesis and anti-inflammation. Owing to the conversion of secretory phenotype, the osteogenic differentiation of bone mesenchymal stem cells was facilitated, and the M1-macrophage-dominant pro-inflammatory microenvironment was ameliorated in osteoporotic bones. Taken together, this study proposed BMEC-targeting nanovesicles treating osteoporosis via converting the skeletal endothelium-associated secretory phenotype.
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Affiliation(s)
- Yongzhi Cui
- Department of Orthopaedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine (originally named Shanghai First People's Hospital), Shanghai 200080, China
| | - Zhongying Li
- Department of Rehabilitation, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, China
| | - Yuanyuan Guo
- Department of Pharmacy, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430077, China
| | - Xiangbei Qi
- Department of Orthopaedics, The Third Hospital, Hebei Medical University, Shijiazhuang, Hebei 050051, China
| | - Yuehua Yang
- Department of Orthopaedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine (originally named Shanghai First People's Hospital), Shanghai 200080, China
| | - Xiong Jia
- Department of Medical Treatment, Shenzhen People's Hospital, Shenzhen, Guangdong 518020, China
| | - Rui Li
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China
| | - Jingyu Shi
- Department of Pharmacy, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430077, China
| | - Weihang Gao
- Department of Orthopaedics, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430077, China
| | - Zhengwei Ren
- Department of Orthopaedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine (originally named Shanghai First People's Hospital), Shanghai 200080, China
| | - Guohui Liu
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China
| | - Qingsong Ye
- Center of Regenerative Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China
| | - Zhiping Zhang
- Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Dehao Fu
- Department of Orthopaedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine (originally named Shanghai First People's Hospital), Shanghai 200080, China
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12
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Bai J, Li L, Kou N, Bai Y, Zhang Y, Lu Y, Gao L, Wang F. Low level laser therapy promotes bone regeneration by coupling angiogenesis and osteogenesis. Stem Cell Res Ther 2021; 12:432. [PMID: 34344474 PMCID: PMC8330075 DOI: 10.1186/s13287-021-02493-5] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Accepted: 07/04/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Bone tissue engineering is a new concept bringing hope for the repair of large bone defects, which remains a major clinical challenge. The formation of vascularized bone is key for bone tissue engineering. Growth of specialized blood vessels termed type H is associated with bone formation. In vivo and in vitro studies have shown that low level laser therapy (LLLT) promotes angiogenesis, fracture healing, and osteogenic differentiation of stem cells by increasing reactive oxygen species (ROS). However, whether LLLT can couple angiogenesis and osteogenesis, and the underlying mechanisms during bone formation, remains largely unknown. METHODS Mouse bone marrow mesenchymal stem cells (BMSCs) combined with biphasic calcium phosphate (BCP) grafts were implanted into C57BL/6 mice to evaluate the effects of LLLT on the specialized vessel subtypes and bone regeneration in vivo. Furthermore, human BMSCs and human umbilical vein endothelial cells (HUVECs) were co-cultured in vitro. The effects of LLLT on cell proliferation, angiogenesis, and osteogenesis were assessed. RESULTS LLLT promoted the formation of blood vessels, collagen fibers, and bone tissue and also increased CD31hiEMCNhi-expressing type H vessels in mBMSC/BCP grafts implanted in mice. LLLT significantly increased both osteogenesis and angiogenesis, as well as related gene expression (HIF-1α, VEGF, TGF-β) of grafts in vivo and of co-cultured BMSCs/HUVECs in vitro. An increase or decrease of ROS induced by H2O2 or Vitamin C, respectively, resulted in an increase or decrease of HIF-1α, and a subsequent increase and decrease of VEGF and TGF-β in the co-culture system. The ROS accumulation induced by LLLT in the co-culture system was significantly decreased when HIF-1α was inhibited with DMBPA and was followed by decreased expression of VEGF and TGF-β. CONCLUSIONS LLLT enhanced vascularized bone regeneration by coupling angiogenesis and osteogenesis. ROS/HIF-1α was necessary for these effects of LLLT. LLLT triggered a ROS-dependent increase of HIF-1α, VEGF, and TGF-β and resulted in subsequent formation of type H vessels and osteogenic differentiation of mesenchymal stem cells. As ROS also was a target of HIF-1α, there may be a positive feedback loop between ROS and HIF-1α, which further amplified HIF-1α induction via the LLLT-mediated ROS increase. This study provided new insight into the effects of LLLT on vascularization and bone regeneration in bone tissue engineering.
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Affiliation(s)
- Jie Bai
- School of Stomatology, Dalian Medical University, Dalian, 116044, China
| | - Lijun Li
- School of Stomatology, Dalian Medical University, Dalian, 116044, China
| | - Ni Kou
- School of Stomatology, Dalian Medical University, Dalian, 116044, China.,The Affiliated Stomatological Hospital of Dalian Medical University School of Stomatology, Dalian, 116027, China
| | - Yuwen Bai
- School of Stomatology, Dalian Medical University, Dalian, 116044, China
| | - Yaoyang Zhang
- School of Stomatology, Dalian Medical University, Dalian, 116044, China
| | - Yun Lu
- School of Stomatology, Dalian Medical University, Dalian, 116044, China.,The Affiliated Stomatological Hospital of Dalian Medical University School of Stomatology, Dalian, 116027, China
| | - Lu Gao
- School of Stomatology, Dalian Medical University, Dalian, 116044, China. .,The Affiliated Stomatological Hospital of Dalian Medical University School of Stomatology, Dalian, 116027, China. .,Academician Laboratory of Immune and Oral Development & Regeneration, Dalian Medical University, Dalian, 116044, China.
| | - Fu Wang
- School of Stomatology, Dalian Medical University, Dalian, 116044, China. .,The Affiliated Stomatological Hospital of Dalian Medical University School of Stomatology, Dalian, 116027, China. .,Academician Laboratory of Immune and Oral Development & Regeneration, Dalian Medical University, Dalian, 116044, China.
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13
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Liang S, Ling S, Du R, Li Y, Liu C, Shi J, Gao J, Sun W, Li J, Zhong G, Liu Z, Zhao D, Sun H, Li Y, Yuan X, Qu H, Jin X, Li D, Shi D, Li Y. The coupling of reduced type H vessels with unloading-induced bone loss and the protection role of Panax quinquefolium saponin in the male mice. Bone 2021; 143:115712. [PMID: 33164873 DOI: 10.1016/j.bone.2020.115712] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 10/20/2020] [Accepted: 10/21/2020] [Indexed: 12/18/2022]
Abstract
Unloading-induced bone loss is a critical complication characterized by the imbalance of bone formation and resorption induced by long-term confinement in bed or spaceflight. CD31hiEmcnhi (type H) vessel is a specific subtype of capillary, which was coupled with osteogenesis. However, the change of type H vessel and its contributions to the unloading-induced bone loss remains undisclosed. Herein, we found that bone formation and the number of type H vessels were synchronously reduced in the hindlimb-unloading (HU) mice. Panax quinquefolium saponin (PQS) could increase bone mass, osteoblast function and the number of type H vessels in the HU mice. In vitro, PQS treatment accelerated HMECs migration, augmented the total tube loops and increased the secretion of VEGF and Noggin. Primary osteoblasts function was obviously increased when treated with supernatant from PQS-treated HMECs. These effects of PQS were substantially counteracted when VEGF and Noggin in HMECs were knocked down by siRNA. These results demonstrated that unloading-induced bone loss is coupled with reduction of type H vessels and PQS performs preventive function via promoting type H vessel angiogenesis, which is closely associated with endothelial cell-derived VEGF and Noggin.
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Affiliation(s)
- Shuai Liang
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China; State Key Lab of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China; Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Shukuan Ling
- State Key Lab of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China
| | - Ruikai Du
- State Key Lab of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China
| | - Yuheng Li
- State Key Lab of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China
| | - Caizhi Liu
- State Key Lab of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China
| | - Junhe Shi
- Center for Wound Healing and Tissue Regeneration, College of Dentistry, University of Illinois at Chicago, 801 S. Paulina Street, Chicago, IL 60612, USA
| | - Jie Gao
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Weijia Sun
- State Key Lab of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China
| | - Jianwei Li
- State Key Lab of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China
| | - Guohui Zhong
- State Key Lab of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China
| | - Zizhong Liu
- State Key Lab of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China
| | - Dingsheng Zhao
- State Key Lab of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China
| | - Huiyuan Sun
- Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China
| | - Yang Li
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences Beijing, Beijing Institute of Lifeomics, Beijing, China
| | - Xinxin Yuan
- State Key Lab of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China
| | - Hua Qu
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xiaoyan Jin
- State Key Lab of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China
| | - Dong Li
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences Beijing, Beijing Institute of Lifeomics, Beijing, China
| | - Dazhuo Shi
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
| | - Yingxian Li
- State Key Lab of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China.
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14
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Zhang J, Pan J, Jing W. Motivating role of type H vessels in bone regeneration. Cell Prolif 2020; 53:e12874. [PMID: 33448495 PMCID: PMC7507571 DOI: 10.1111/cpr.12874] [Citation(s) in RCA: 96] [Impact Index Per Article: 19.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Revised: 06/03/2020] [Accepted: 06/22/2020] [Indexed: 02/06/2023] Open
Abstract
Coupling between angiogenesis and osteogenesis has an important role in both normal bone injury repair and successful application of tissue‐engineered bone for bone defect repair. Type H blood vessels are specialized microvascular components that are closely related to the speed of bone healing. Interactions between type H endothelial cells and osteoblasts, and high expression of CD31 and EMCN render the environment surrounding these blood vessels rich in factors conducive to osteogenesis and promote the coupling of angiogenesis and osteogenesis. Type H vessels are mainly distributed in the metaphysis of bone and densely surrounded by Runx2+ and Osterix+ osteoprogenitors. Several other factors, including hypoxia‐inducible factor‐1α, Notch, platelet‐derived growth factor type BB, and slit guidance ligand 3 are involved in the coupling of type H vessel formation and osteogenesis. In this review, we summarize the identification and distribution of type H vessels and describe the mechanism for type H vessel‐mediated modulation of osteogenesis. Type H vessels provide new insights for detection of the molecular and cellular mechanisms that underlie the crosstalk between angiogenesis and osteogenesis. As a result, more feasible therapeutic approaches for treatment of bone defects by targeting type H vessels may be applied in the future.
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Affiliation(s)
- Jiankang Zhang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Jian Pan
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Wei Jing
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China
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15
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Xu GP, Zhang XF, Sun L, Chen EM. Current and future uses of skeletal stem cells for bone regeneration. World J Stem Cells 2020; 12:339-350. [PMID: 32547682 PMCID: PMC7280866 DOI: 10.4252/wjsc.v12.i5.339] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2020] [Revised: 04/07/2020] [Accepted: 04/18/2020] [Indexed: 02/06/2023] Open
Abstract
The postnatal skeleton undergoes growth, modeling, and remodeling. The human skeleton is a composite of diverse tissue types, including bone, cartilage, fat, fibroblasts, nerves, blood vessels, and hematopoietic cells. Fracture nonunion and bone defects are among the most challenging clinical problems in orthopedic trauma. The incidence of nonunion or bone defects following fractures is increasing. Stem and progenitor cells mediate homeostasis and regeneration in postnatal tissue, including bone tissue. As multipotent stem cells, skeletal stem cells (SSCs) have a strong effect on the growth, differentiation, and repair of bone regeneration. In recent years, a number of important studies have characterized the hierarchy, differential potential, and bone formation of SSCs. Here, we describe studies on and applications of SSCs and/or mesenchymal stem cells for bone regeneration.
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Affiliation(s)
- Guo-Ping Xu
- Department of Orthopedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
| | - Xiang-Feng Zhang
- Department of Orthopedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
| | - Lu Sun
- Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Harvard University, Boston, MA 02115, United States
| | - Er-Man Chen
- Department of Orthopedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
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16
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Chen Y, Yu H, Zhu D, Liu P, Yin J, Liu D, Zheng M, Gao J, Zhang C, Gao Y. miR-136-3p targets PTEN to regulate vascularization and bone formation and ameliorates alcohol-induced osteopenia. FASEB J 2020; 34:5348-5362. [PMID: 32072664 DOI: 10.1096/fj.201902463rr] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Revised: 02/01/2020] [Accepted: 02/05/2020] [Indexed: 12/11/2022]
Abstract
Alcohol consumption is regarded as one of the leading risk factors for secondary osteopenia. Coupled angiogenesis and osteogenesis via distinct type-H vessels orchestrates subtle biological processes of bone homeostasis. The dysfunction of angiogenesis and osteogenesis contributes to decreased bone mass during the development of osteopenia. Herein, we identified microRNA-136-3p was remarkedly downregulated in the mouse model of alcohol-induced osteopenia. Following the alcohol administration, downregulated microRNA-136-3p significantly suppressed vascularization and osteogenic differentiation in human umbilical vein endothelial cells (HUVECs) and bone mesenchymal stem cells (BMSCs), respectively. Furthermore, microRNA-136-3p could target phosphatase and tensin homolog deleted on chromosome ten (PTEN) in both HUVECs and BMSCs, thus substantially modulating the capacity of vessel formation and osteogenic differentiation. In the mouse model, microRNA-136-3p Agomir ameliorated alcohol-induced osteopenia, with the concomitant restoration of bone mass and type-H vessel formation. For the first time, this study demonstrated the pivotal role of microRNA-136-3p/PTEN axis in regulations of vascularization and bone formation, which might become the potential therapeutic target of alcohol-induced bone loss.
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Affiliation(s)
- Yixuan Chen
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Hongping Yu
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Daoyu Zhu
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Pei Liu
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Junhui Yin
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.,Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Delin Liu
- Centre for Orthopaedic Translational Research, Medical School, University of Western Australia, Nedlands, WA, Australia
| | - Minghao Zheng
- Centre for Orthopaedic Translational Research, Medical School, University of Western Australia, Nedlands, WA, Australia.,Perron Institute for Neurological and Translational Science, Nedlands, WA, Australia
| | - Junjie Gao
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.,Centre for Orthopaedic Translational Research, Medical School, University of Western Australia, Nedlands, WA, Australia.,Perron Institute for Neurological and Translational Science, Nedlands, WA, Australia
| | - Changqing Zhang
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.,Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Youshui Gao
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.,Centre for Orthopaedic Translational Research, Medical School, University of Western Australia, Nedlands, WA, Australia.,Perron Institute for Neurological and Translational Science, Nedlands, WA, Australia
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17
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Miao Y, Chen Y, Liu X, Diao J, Zhao N, Shi X, Wang Y. Melatonin decorated 3D-printed beta-tricalcium phosphate scaffolds promoting bone regeneration in a rat calvarial defect model. J Mater Chem B 2019. [DOI: 10.1039/c8tb03361g] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
3D-printed β-TCP scaffolds decorated with melatonin via dopamine mussel-inspired chemistry enhance the osteogenesis and in vivo bone regeneration.
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Affiliation(s)
- Yali Miao
- School of Materials Science and Engineering
- South China University of Technology
- Guangzhou 510640
- China
- National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology
| | - Yunhua Chen
- School of Materials Science and Engineering
- South China University of Technology
- Guangzhou 510640
- China
- National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology
| | - Xiao Liu
- Key Laboratory of Biomedical Engineering of Guangdong Province, and Innovation Center for Tissue Restoration and Reconstruction, South China University of Technology
- Guangzhou 510006
- China
- Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology
- Guangzhou 510006
| | - Jingjing Diao
- Key Laboratory of Biomedical Engineering of Guangdong Province, and Innovation Center for Tissue Restoration and Reconstruction, South China University of Technology
- Guangzhou 510006
- China
- Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology
- Guangzhou 510006
| | - Naru Zhao
- School of Materials Science and Engineering
- South China University of Technology
- Guangzhou 510640
- China
- National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology
| | - Xuetao Shi
- National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology
- Guangzhou 510006
- China
- Key Laboratory of Biomedical Engineering of Guangdong Province, and Innovation Center for Tissue Restoration and Reconstruction, South China University of Technology
- Guangzhou 510006
| | - Yingjun Wang
- National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology
- Guangzhou 510006
- China
- Key Laboratory of Biomedical Engineering of Guangdong Province, and Innovation Center for Tissue Restoration and Reconstruction, South China University of Technology
- Guangzhou 510006
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18
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Bai L, Du Z, Du J, Yao W, Zhang J, Weng Z, Liu S, Zhao Y, Liu Y, Zhang X, Huang X, Yao X, Crawford R, Hang R, Huang D, Tang B, Xiao Y. A multifaceted coating on titanium dictates osteoimmunomodulation and osteo/angio-genesis towards ameliorative osseointegration. Biomaterials 2018; 162:154-169. [PMID: 29454274 DOI: 10.1016/j.biomaterials.2018.02.010] [Citation(s) in RCA: 163] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2017] [Revised: 01/15/2018] [Accepted: 02/02/2018] [Indexed: 12/15/2022]
Abstract
A multifaceted coating for hard tissue implants, with favorable osteogenesis, angiogenesis, and osteoimmunomodulation abilities, would be of great value since it could improve osseointegration and alleviate prosthesis loosening. However, to date there are few coatings that fully satisfy these criteria. Herein we describe a microporous TiO2 coating decorated with hydroxyapatite (HA) nanoparticles that is generated by micro-arc oxidation of pure titanium (Ti) and followed annealing. By altering the annealing temperature, it is possible to simultaneously tune the coating's physical (morphology and wettability) and chemical (composites and crystallinity) properties. A coating produced with micro-arc oxidization (MAO) with an annealing temperature of 650 °C (MAO-650) exhibits numerous favorable physicochemical properties, such as hybrid micro-nano morphology, superhydrophilicity, and highly crystalline HA nanoparticles. In vitro experiments reveal that the MAO-650 coating not only supports proliferation and differentiation of both osteoblasts and endothelial cells, but also inhibits the inflammatory response of macrophages and enables a favorable osteoimmunomodulation to facilitate osteo/angio-genesis. In vivo evaluation mirrors these results, and shows that the MAO-650 coating results in ameliorative osseointegration when compared with the pristine MAO coating. These data highlight the profound effect of surface physicochemical properties on the regulation of osteo/angio-genesis and osteoimmunomodulation in the enhancement of osseointegration.
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Affiliation(s)
- Long Bai
- Research Institute of Surface Engineering, Taiyuan University of Technology, Taiyuan, China; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, 4059, Australia; Australia-China Centre for Tissue Engineering and Regenerative Medicine, Queensland University of Technology, Brisbane, 4059, Australia
| | - Zhibin Du
- Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, 4059, Australia; Australia-China Centre for Tissue Engineering and Regenerative Medicine, Queensland University of Technology, Brisbane, 4059, Australia
| | - Jingjing Du
- Department of Biomedical Engineering, Research Center for Nano-biomaterials and Regenerative Medicine, College of Mechanics, Taiyuan University of Technology, Taiyuan, China
| | - Wei Yao
- College and Hospital of Stomatology, Shanxi Medical University, Taiyuan, China
| | - Jiaming Zhang
- Research Institute of Surface Engineering, Taiyuan University of Technology, Taiyuan, China
| | - Zeming Weng
- Research Institute of Surface Engineering, Taiyuan University of Technology, Taiyuan, China
| | - Si Liu
- Research Institute of Surface Engineering, Taiyuan University of Technology, Taiyuan, China
| | - Ya Zhao
- Research Institute of Surface Engineering, Taiyuan University of Technology, Taiyuan, China
| | - Yanlian Liu
- Research Institute of Surface Engineering, Taiyuan University of Technology, Taiyuan, China
| | - Xiangyu Zhang
- Research Institute of Surface Engineering, Taiyuan University of Technology, Taiyuan, China
| | - Xiaobo Huang
- Research Institute of Surface Engineering, Taiyuan University of Technology, Taiyuan, China
| | - Xiaohong Yao
- Research Institute of Surface Engineering, Taiyuan University of Technology, Taiyuan, China
| | - Ross Crawford
- Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, 4059, Australia; Australia-China Centre for Tissue Engineering and Regenerative Medicine, Queensland University of Technology, Brisbane, 4059, Australia
| | - Ruiqiang Hang
- Research Institute of Surface Engineering, Taiyuan University of Technology, Taiyuan, China.
| | - Di Huang
- Department of Biomedical Engineering, Research Center for Nano-biomaterials and Regenerative Medicine, College of Mechanics, Taiyuan University of Technology, Taiyuan, China.
| | - Bin Tang
- Research Institute of Surface Engineering, Taiyuan University of Technology, Taiyuan, China
| | - Yin Xiao
- Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, 4059, Australia; Australia-China Centre for Tissue Engineering and Regenerative Medicine, Queensland University of Technology, Brisbane, 4059, Australia.
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19
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Geng Z, Wang X, Zhao J, Li Z, Ma L, Zhu S, Liang Y, Cui Z, He H, Yang X. The synergistic effect of strontium-substituted hydroxyapatite and microRNA-21 on improving bone remodeling and osseointegration. Biomater Sci 2018; 6:2694-2703. [DOI: 10.1039/c8bm00716k] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Surgical failure, mainly caused by loosening implants, causes great mental and physical trauma to patients.
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20
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Wang L, Jia P, Shan Y, Hao Y, Wang X, Jiang Y, Yuan Y, Du Q, Zhang H, Yang F, Zhang W, Sheng M, Xu Y. Synergistic protection of bone vasculature and bone mass by desferrioxamine in osteoporotic mice. Mol Med Rep 2017; 16:6642-6649. [PMID: 28901524 PMCID: PMC5865796 DOI: 10.3892/mmr.2017.7451] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2017] [Accepted: 08/16/2017] [Indexed: 01/07/2023] Open
Abstract
It has previously been demonstrated that impaired angiogenesis is associated with metabolic abnormalities in bone in addition to osteoporosis (including postmenopausal osteoporosis). Enhancing vessel formation in bone is therefore a potential clinical therapy for osteoporosis. The present study conducted an in-depth investigation using desferrioxamine (DFO) in an ovariectomy (OVX)-induced osteoporotic mouse model in order to determine the time frame of alteration of bone characteristics and the therapeutic effect of DFO. It was demonstrated that OVX induced instant bone mass loss 1 week following surgery, as expected. In contrast, DFO treatment protected the mice against OVX-induced osteoporosis during the first week, however failed to achieve long-term protection at a later stage. A parallel alteration for cluster of differentiation 31/endomucin double positive vessels (type H vessels) was observed, which have previously been reported to be associated with osteogenesis. DFO administration not only partially prevented bone loss and maintained trabecular bone microarchitecture, however additionally enhanced the type H vessels during the first week post-OVX. The molecular mechanism of how DFO influences type H vessels to regulate bone metabolism needs to be further investigated. However, the findings of the present study provide preliminary evidence to support combined vascular and osseous therapies for osteoporotic patients. Pharmacotherapy may offer a novel target for improving osteoporosis by promoting type H vessel formation, which indicates potential clinical significance in the field of bone metabolism.
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Affiliation(s)
- Liang Wang
- Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China
| | - Peng Jia
- Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China
| | - Yu Shan
- Department of Orthopaedics, The First People's Hospital of Wujiang, Suzhou, Jiangsu 215200, P.R. China
| | - Yanming Hao
- Department of Orthopaedics, The First People's Hospital of Kunshan, Suzhou, Jiangsu 215300, P.R. China
| | - Xiao Wang
- Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China
| | - Yu Jiang
- Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China
| | - Ye Yuan
- Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China
| | - Qiaoqiao Du
- Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China
| | - Hui Zhang
- Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China
| | - Fan Yang
- Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China
| | - Wen Zhang
- Orthopaedic Institute of Soochow University, Suzhou, Jiangsu 215006, P.R. China
| | - Mao Sheng
- Department of Radiology, Children's Hospital of Soochow University, Suzhou, Jiangsu 215123, P.R. China
| | - Youjia Xu
- Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China
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21
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Abstract
The extent of ageing in the musculoskeletal system during the life course affects the quality and length of life. Loss of bone, degraded articular cartilage, and degenerate, narrowed intervertebral discs are primary features of an ageing skeleton, and together they contribute to pain and loss of mobility. This review covers the cellular constituents that make up some key components of the musculoskeletal system and summarizes discussion from the 2015 Aarhus Regenerative Orthopaedic Symposium (AROS) (Regeneration in the Ageing Population) about how each particular cell type alters within the ageing skeletal microenvironment.
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Affiliation(s)
- Sally Roberts
- Spinal Studies and ISTM, Keele University, and Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust, Oswestry, UK
| | - Pauline Colombier
- INSERM U791-LIOAD, Centre Hospitalo-Universitaire (CHU) de Nantes, Nantes, France
| | - Aneka Sowman
- Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - Claire Mennan
- Spinal Studies and ISTM, Keele University, and Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust, Oswestry, UK
| | - Jan H D Rölfing
- Orthopaedic Research Laboratory and Departments of Orthopaedics, Aarhus and Aalborg University Hospitals, Aarhus, Denmark
| | - Jérôme Guicheux
- INSERM U791-LIOAD, Centre Hospitalo-Universitaire (CHU) de Nantes, Nantes, France
| | - James R Edwards
- Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK,Correspondence:
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Calcium Phosphates and Angiogenesis: Implications and Advances for Bone Regeneration. Trends Biotechnol 2016; 34:983-992. [PMID: 27481474 DOI: 10.1016/j.tibtech.2016.07.005] [Citation(s) in RCA: 95] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2016] [Revised: 07/13/2016] [Accepted: 07/14/2016] [Indexed: 01/10/2023]
Abstract
Calcium phosphates (CaPs) are among the most utilized synthetic biomaterials for bone regeneration, largely owing to their established osteoconductive and osteoinductive properties. While angiogenesis is a crucial prerequisite to bone formation, research and applications for CaPs have not appreciated its crucial role. This review discusses how CaPs influence angiogenesis, and highlights promising strategies that address this topic. The objective is to draw attention to the gap in the literature and to highlight the importance of angiogenesis in CaP research, development, and use.
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Lv J, Xiu P, Tan J, Jia Z, Cai H, Liu Z. Enhanced angiogenesis and osteogenesis in critical bone defects by the controlled release of BMP-2 and VEGF: implantation of electron beam melting-fabricated porous Ti
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V scaffolds incorporating growth factor-doped fibrin glue. Biomed Mater 2015; 10:035013. [DOI: 10.1088/1748-6041/10/3/035013] [Citation(s) in RCA: 85] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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24
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Abstract
Hypoxia-inducible factor (HIF) signalling is intricately involved in coupling angiogenesis and osteogenesis during bone development and repair. Activation of HIFs in response to a hypoxic bone micro-environment stimulates the transcription of multiple genes with effects on angiogenesis, precursor cell recruitment and differentiation. Substantial progress has been made in our understanding of the molecular mechanisms by which oxygen content regulates the levels and activity of HIFs. In particular, the discovery of the role of oxygen-dependent hydroxylase enzymes in modulating the activity of HIF-1α has sparked interest in potentially promising therapeutic strategies in multiple clinical fields and most recently bone healing. Several small molecules, termed hypoxia mimics, have been identified as activators of the HIF pathway and have demonstrated augmentation of both bone vascularity and bone regeneration in vivo. In this review we discuss key elements of the hypoxic signalling pathway and its role in bone regeneration. Current strategies for the manipulation of this pathway for enhancing bone repair are presented with an emphasis on recent pre-clinical in vivo investigations. These findings suggest promising approaches for the development of therapies to improve bone repair and tissue engineering strategies.
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25
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Aeimlapa R, Wongdee K, Charoenphandhu N, Suntornsaratoon P, Krishnamra N. Premature chondrocyte apoptosis and compensatory upregulation of chondroregulatory protein expression in the growth plate of Goto-Kakizaki diabetic rats. Biochem Biophys Res Commun 2014; 452:395-401. [PMID: 25159845 DOI: 10.1016/j.bbrc.2014.08.085] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2014] [Accepted: 08/18/2014] [Indexed: 12/28/2022]
Abstract
Type 2 diabetes mellitus (T2DM) is much more detrimental to bone than previously thought. Specifically, it is associated with aberrant bone remodeling, defective bone microstructure, poor bone quality, and growth retardation. The T2DM-associated impairment of bone elongation may result from a decrease in growth plate function, but the detailed mechanism has been unknown. The present study, therefore, aimed to test hypothesis that T2DM led to premature apoptosis of growth plate chondrocytes in Goto-Kakizaki (GK) type 2 diabetic rats, and thus triggered the compensatory responses to overcome this premature apoptosis, such as overexpression of Runt-related transcription factor (Runx)-2 and vascular endothelial growth factor (VEGF), the essential mediators for bone elongation. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) of epiphyseal sections successfully revealed increases in chondrocyte apoptosis in the hypertrophic zone (HZ) and chondro-osseous junction of GK rats. Quantitative immunohistochemical analysis further confirmed the overexpression of parathyroid hormone-related protein (PTHrP), Runx2 and VEGF, but not Indian hedgehog (Ihh) in the HZ. Analysis of blood chemistry indicated suppression of bone remodeling with a marked decrease in parathyroid hormone level. In conclusion, GK rats manifested a premature increase in chondrocyte apoptosis in the HZ of growth plate, and a compensatory overexpression of chondroregulatory proteins, such as PTHrP, Runx2, and VEGF. Our results, therefore, help explain how T2DM leads to impaired bone elongation and growth retardation.
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Affiliation(s)
- Ratchaneevan Aeimlapa
- Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand; Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University, Bangkok, Thailand
| | - Kannikar Wongdee
- Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University, Bangkok, Thailand; Office of Academic Management, Faculty of Allied Health Sciences, Burapha University, Chonburi, Thailand.
| | - Narattaphol Charoenphandhu
- Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand; Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University, Bangkok, Thailand
| | - Panan Suntornsaratoon
- Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand; Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University, Bangkok, Thailand
| | - Nateetip Krishnamra
- Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand; Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University, Bangkok, Thailand
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