Background: Bone formation and homeostasis are greatly dependent on the osteogenic differentiation of human bone marrow stem cells (BMSCs). Therefore, revealing the mechanisms underlying osteogenic differentiation of BMSCs will provide new candidate therapeutic targets for osteoporosis.
Methods: The osteogenic differentiation of BMSCs was measured by analyzing ALP activity and expression levels of osteogenic markers. Cellular Fe and ROS levels and cell viability were applied to evaluate the ferroptosis of BMSCs. qRT-PCR, Western blotting, and co-immunoprecipitation assays were harnessed to study the molecular mechanism.
Results: The mRNA level of CRYAB was decreased in the plasma of osteoporosis patients. Overexpression of CRYAB increased the expression of osteogenic markers including OCN, OPN, RUNX2, and COLI, and also augmented the ALP activity in BMSCs, on the contrary, knockdown of CRYAB had opposite effects. IP-MS technology identified CRYAB-interacted proteins and further found that CRYAB interacted with ferritin heavy chain 1 (FTH1) and maintained the stability of FTH1 via the proteasome mechanism. Mechanically, we unraveled that CRYAB regulated FTH1 protein stability in a lactylation-dependent manner. Knockdown of FTH1 suppressed the osteogenic differentiation of BMSCs, and increased the cellular Fe and ROS levels, and eventually promoted ferroptosis. Rescue experiments revealed that CRYAB suppressed ferroptosis and promoted osteogenic differentiation of BMSCs via regulating FTH1. The mRNA level of FTH1 was decreased in the plasma of osteoporosis patients.
Conclusions: Downregulation of CRYAB boosted FTH1 degradation and increased cellular Fe and ROS levels, and finally improved the ferroptosis and lessened the osteogenic differentiation of BMSCs.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11164484 | PMC |
| http://dx.doi.org/10.18632/aging.205851 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Guidance on the assessment of the functionality of biomaterials for periodontal tissue regeneration: Methodologies and testing procedures.
Dent Mater
January 2025
Department of Cariology, Restorative Sciences and Endodontics, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA; Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address:
Innovative biomaterials and tissue engineering strategies show great promise in regenerating periodontal tissues. This guidance provides an overview and detailed recommendations for evaluating the biological functionality of these new biomaterials in vitro, focusing on mineralization, immunomodulatory effects, cellular differentiation, and angiogenesis. Additionally, it discusses the use of in vivo experimental models that mimic periodontitis and scrutinizes methods such as osteogenic differentiation, immunomodulation, and anti-inflammatory responses to assess the effectiveness of these biomaterials in promoting periodontal tissue reconstruction.
View Article and Find Full Text PDFIntegrated GelMA and liposome composite hydrogel with effective coupling of angiogenesis and osteogenesis for promoting bone regeneration.
Int J Biol Macromol
January 2025
Department of Orthopedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, PR China. Electronic address:
In clinical scenarios, bone defects stemming from trauma, infections, degenerative diseases, or hereditary conditions necessitate considerable bone grafts. Researchers ardently focus on creating diverse biomaterials to expedite and enhance these intricate restorative processes. These biomaterials play a pivotal role in aiding osteogenesis and angiogenesis factors for reconstructing stable, fully developed bone tissue.
View Article and Find Full Text PDFAn emodin-mediated multifunctional nanoplatform with augmented sonodynamic and immunoregulation for osteomyelitis therapy.
J Colloid Interface Sci
January 2025
Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan 030032 China; Shanxi Provincial Key Laboratory for Translational Nuclear Medicine and Precision Protection, Taiyuan 030006 China. Electronic address:
Emodin (ED), as a traditional Chinese medicine, possesses a variety of biological activities and is also one of natural sonosensitizer. Whether emodin could react with titanium dioxide to enhance the sonodynamic activity for safely treating osteomyelitis remains to be explored. Hence, an ED-conjugated Mn-doped titanium dioxide (TOM) nanorod array is designed and prepared on titanium to eliminate bacterial infections under ultrasound (US) treatment.
View Article and Find Full Text PDFComprehensive three-dimensional microCT and signaling analysis reveal the teratogenic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on craniofacial bone development in mice.
Ecotoxicol Environ Saf
January 2025
Department of Stomatology, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, No. 242, Guangji Road, Suzhou, Jiangsu Province 215000, China. Electronic address:
Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in utero can result in osteogenic defect during palatogenesis, but the effects on other craniofacial bones and underlying mechanisms remain to be characterized. By treating pregnant mice with TCDD (40 μg/kg) at the vital craniofacial patterning stages (embryonic day 8.5, 10.
View Article and Find Full Text PDFAucubin Promotes BMSCs Proliferation and Differentiation of Postmenopausal Osteoporosis Patients by Regulating Ferroptosis and BMP2 Signalling.
J Cell Mol Med
January 2025
Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Postmenopausal osteoporosis (PMOP) is a chronic systemic bone metabolism disorder. Promotion in the patterns of human bone marrow mesenchymal stem cells (hBMSCs) differentiation towards osteoblasts contributes to alleviating osteoporosis. Aucubin, a natural compound isolated from the well-known herbal medicine Eucommia, was previously shown to possess various pharmacological effects.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!