Year: 2021
Type: article
Abstract: Atrophic fracture nonunion poses a significant clinical problem with limited therapeutic interventions. In this study, we developed a unique nonunion model with high clinical relevance using serum transfer-induced rheumatoid arthritis (RA). Arthritic mice displayed fracture nonunion with the absence of fracture callus, diminished angiogenesis and fibrotic scar tissue formation leading to the failure of biomechanical properties, representing the major manifestations of atrophic nonunion in the clinic. Mechanistically, we demonstrated that the angiogenesis defect observed in RA mice was due to the downregulation of SPP1 and CXCL12 in chondrocytes, as evidenced by the restoration of angiogenesis upon SPP1 and CXCL12 treatment in vitro. In this regard, we developed a biodegradable scaffold loaded with SPP1 and CXCL12, which displayed a beneficial effect on angiogenesis and fracture repair in mice despite the presence of inflammation. Hence, these findings strongly suggest that the sustained release of SPP1 and CXCL12 represents an effective therapeutic approach to treat impaired angiogenesis and fracture nonunion under inflammatory conditions.
Source: Bone Research
Authors: Cuicui Wang, Jun Ying, Xiaolei Nie, Tianhong Zhou, Ding Xiao, Gaurav Swarnkar, Yousef Abu-Amer, Jianjun Guan, Jie Shen
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,890
Funders: U.S. Department of Health and Human Services, Shriners Hospitals for Children, National Institutes of Health, Musculoskeletal Research Center, Washington University in St. Louis, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Biomedical Imaging and Bioengineering
Awards: G1151567102, G124952752, Hydrogel encapsulation of a tissue repair protein to treat chronic wounds, G1394730555, G2310844859, G2330615755, CONTROL OF CARDIAC FIBROSIS TO PREVENT CARDIAC FUNCTION DETERIORATION, G2472603119, G2729652715, Preservation and Vascularization of Cardiac Extracellular Matrix after Myocardial Infarction, G2775599718, Stem cell oxygenation and ischemic tissue regeneration, G294724927, G3150881056, G3471694253, G3690325005, G3881430303, G3887036009, G391394221, Regulatory Mechanisms of Implant-Induced Osteolysis, G4009827160, Mechanisms of Physiologic and Pathologic Osteoclastogenesis, G4141707219, Stem cell therapy for fracture nonunion under inflammatory diseases, G4365017791, G4461453974, G4790721331, G5634881710, G5696530169, G5721150043, G5840076957, G5960459233, G7008996325, G7046208010, G717714865, G758673566, G7659721888, G7677371269, Epigenetic Regulation of Bone Regeneration in Inflammatory Disease, G8885355438, G9000005404, G9000125016, G9000161266, G9000206488, G9000217772, Targeting angiogenesis for fracture nonunion treatment under inflammatory diseases
OpenAlex ID: W3170774376