Morgan McAdams

Introduction. Osteonecrosis of the femoral head is a bone lesion characterized by disruption of circulation, which leads to a decrease in bone growth and increased fat deposition.⁸ A lack of effective noninvasive treatments has led to the exploration of mesenchymal stem cell exosomes as a potential therapeutic tool.^7-8 Exosomes are extracellular vesicles that contain proteins and micro-RNAs, which are absorbed by surrounding cells to enact a physiologic response.⁷ Recent studies have revealed that dysregulation of VEGF and BMP-2 expression and the Hippo signaling pathway play a key role in pathogenesis of this disease.^1-2 Furthermore, exosomes can be used to target and upregulate these osteogenic pathways.^4-7,9  Methods. C3H10T1/2 (MSC-like progenitor) cell cultures were treated with FGF2. To determine the effect of FGF2 on osteogenesis and TAZ, several procedures were performed. These included actinomycin treatment to quantify TAZ expression, immunocytochemical analysis to determine the localization of TAZ, and western blot and qRT-PCR analysis to quantify the interaction between TAZ and Runx2.¹ Hydroxyapatite scaffolds were used to mimic human trabecular bone, loaded with MC3T3-E1 (osteoblast precursor) cells, and treated with VEGF and BMP-2. Micro-CT imaging with stained sections and immunochemical staining were used to determine gross and microscopic effects.² Prednisolone acetate was injected twice a week to establish SNFH in rats. HucMSC-exosomes were injected into the marrow cavity of the experimental group. General influences of hucMSC-exosomes on the joint were examined by H&E and TUNEL staining techniques. The expression of BMP-2 and VEGF were measured using immunohistochemical staining, RT-PCR, and western blotting.⁶ HucMSC-exosomes containing miR-365a-5p were injected into the marrow cavity of rats with GIONFH. Micro-CT was used to examine gross effects, Targetscan database was determined the degree of interaction between miR-365a-5p and SAV1, and western blot analysis was utilized to detect downstream effects on the Hippo pathway.⁵ Results. TAZ was shown to be upregulated, localized within the nucleus, and have an increased interaction with Runx2.¹ VEGF and BMP-2 were shown to increase lectin and collagen type 1 expression and stimulate new bone growth.² HucMSC-exosomes were found to increase VEGF and BMP-2 expression, fibrous callus formation, and trabecular bone structure.⁶ MiR-365a-5p was found to interact with SAV1, which subsequently upregulated TAZ, increased osteogenic marker expression, and increased trabecular bone repair.⁵ Conclusion. These findings indicate that dysregulation of these pathways is important in the pathogenesis of osteonecrosis and that exosomes can be used to target these pathways for treatment.^1-2,5-6

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