Promotion of Bone Formation in a Rat Osteoporotic Vertebral Body Defect Model via Suppression of Osteoclastogenesis by Ectopic Embryonic Calvaria Derived Mesenchymal Stem Cells.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Osteogenesis* ; Mesenchymal Stem Cells*/metabolism ; Mesenchymal Stem Cells*/cytology ; Skull*/pathology ; Cell Differentiation* ; Disease Models, Animal* ; Osteoporosis*/pathology ; Osteoporosis*/metabolism ; Osteoporosis*/therapy; Animals ; Rats ; Mice ; Female ; RAW 264.7 Cells ; Osteoclasts/metabolism ; Bone Regeneration ; Rats, Sprague-Dawley ; Mesenchymal Stem Cell Transplantation/methods ; Vertebral Body/metabolism ; X-Ray Microtomography ; Osteoporotic Fractures/therapy ; Osteoporotic Fractures/metabolism ; Osteoporotic Fractures/pathology

Osteoporotic vertebral compression fractures (OVCFs) are the most prevalent fractures among patients with osteoporosis, leading to severe pain, deformities, and even death. This study explored the use of ectopic embryonic calvaria derived mesenchymal stem cells (EE-cMSCs), which are known for their superior differentiation and proliferation capabilities, as a potential treatment for bone regeneration in OVCFs. We evaluated the impact of EE-cMSCs on osteoclastogenesis in a RAW264.7 cell environment, which was induced by the receptor activator of nuclear factor kappa-beta ligand (RANKL), using cytochemical staining and quantitative real-time PCR. The osteogenic potential of EE-cMSCs was evaluated under various hydrogel conditions. An osteoporotic vertebral body bone defect model was established by inducing osteoporosis in rats through bilateral ovariectomy and creating defects in their coccygeal vertebral bodies. The effects of EE-cMSCs were examined using micro-computed tomography (μCT) and histology, including immunohistochemical analyses. In vitro, EE-cMSCs inhibited osteoclast differentiation and promoted osteogenesis in a 3D cell culture environment using fibrin hydrogel. Moreover, μCT and histological staining demonstrated increased new bone formation in the group treated with EE-cMSCs and fibrin. Immunostaining showed reduced osteoclast activity and bone resorption, alongside increased angiogenesis. Thus, EE-cMSCs can effectively promote bone regeneration and may represent a promising therapeutic approach for treating OVCFs.

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27304C0002 United States ES NIEHS NIH HHS; 27306C0002 United States ES NIEHS NIH HHS; 22C0604L1 and 21C0725L1-11. Korea government (the Ministry of Science and ICT, the Ministry of Health & Welfare); HR16C0002 Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Wel-fare, Republic of Korea

Keywords: bone regeneration; ectopic embryonic calvaria derived mesenchymal stem cell; mesenchymal stem cell; osteogenesis; osteoporosis; osteoporotic vertebral compression fracture

Date Created: 20240810 Date Completed: 20240810 Latest Revision: 20240923

20240923

PMC11311643

10.3390/ijms25158174

39125746