The Effects of Fluvastatin on Indian Hedgehog Pathway in Endochondral Ossification
| Autor: | Takenobu Ishii, Taiki Morikawa, Yuki Iijima, Munetada Ishikawa, Kenji Sueishi |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Indian hedgehog Statin medicine.drug_class Biomedical Engineering Physical Therapy Sports Therapy and Rehabilitation Biology Mice 03 medical and health sciences 0302 clinical medicine Osteogenesis Internal medicine medicine Animals Immunology and Allergy Hedgehog Proteins Fluvastatin Endochondral ossification Clinical Research papers 030203 arthritis & rheumatology Parathyroid hormone-related protein Cell growth Wnt signaling pathway Cell Differentiation Fibroblast growth factor receptor 3 biology.organism_classification body regions 030104 developmental biology Endocrinology Immunostaining Signal Transduction |
| Zdroj: | Cartilage |
| ISSN: | 1947-6043 1947-6035 |
| DOI: | 10.1177/1947603519862318 |
| Popis: | Statins have demonstrated to be effective for treating chondrodysplasia and its effects were believed to be associated with the fibroblast growth factor receptor 3 (FGFR3). Statins promoted the degradation of FGFR3 in studies using disease-specific induced pluripotent stem cells and model mice, however, recent studies using normal chondrocytes reported that statins did not degrade FGFR3. In order to further investigate the effects of statins in endochondral ossification, this study examined the influence of statins on Indian hedgehog (Ihh), another important component of endochondral ossification, and its related pathways. The chondrocyte cell line ATDC5 was used to investigate changes in cell proliferation, mRNA, and protein expression levels. In addition, an organ culture of a mouse metatarsal bone was performed followed by hematoxylin-eosin staining and fluorescent immunostaining. Results indicated that expression level of Ihh increased with the addition of statins, which activated the Ihh pathway and altered the localization of Ihh. Changes in cholesterol modification may have affected Ihh diffusibility; however, further experiments are necessary. A reactive increase in parathyroid hormone–related protein (PTHrP) was observed in addition to changes in the Wnt pathway through secreted-related protein 2/3 and low-density lipoprotein 5/6. This led to the promotion of cell proliferation, increase of the hypertrophic chondrocyte layer, inhibition of apoptosis, and decrease in mineralization. This study demonstrated that statins had an influence on Ihh, and that the hyperfunction of Ihh may prevent premature cell death caused by FGFR3-related chondrodysplasia through an indirect increase in the expression of PTHrP. |
| Databáze: | OpenAIRE |
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