2023 Fiscal Year Final Research Report
Development of a novel co-culture system to evaluate human osteoclast differentiation
| Project/Area Number |
21K09284
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 56020:Orthopedics-related
|
|---|
| Research Institution | Jichi Medical University |
|---|
Principal Investigator |
Sato Kojiro 自治医科大学, 医学部, 教授 (10372434)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
小又 尉広 自治医科大学, 医学部, 客員研究員 (20644371)
|
|---|
| Project Period (FY) |
2021-04-01 – 2024-03-31
|
| Keywords | 破骨細胞 / RANKL / TNF |
|---|
| Outline of Final Research Achievements |
As an in vitro differentiation system for human osteoclasts, peripheral blood-derived classical monocytes were cultured in the presence of (i) M-CSF (ii) GM-CSF (iii) GM-CSF + IL-4 (iv) GM-CSF + TNF as progenitor cells and further cultured in the presence of M-CS+RANKL. By adding GM-CSF, IL-4, and TNF to the second step, the effects of these cytokines on osteoclastogenesis were also examined.
Although multinuclear cell differentiation was observed in the presence of TNF and GM-CSF, IL-4 strongly inhibited osteoclastogenesis. This suggests that if IL-4 is involved in the differentiation of osteoclast progenitor cells, the environment must be completely independent of that of osteoclast differentiation.
|
| Free Research Field |
臨床免疫学
|
| Academic Significance and Societal Importance of the Research Achievements |
関節リウマチ(RA)の病態において観察される破骨細胞分化はいくつかの点で生理的な破骨細胞分化と異なると考えられる。RAの治療にパラダイム・シフトをもたらしたTNF阻害薬が破骨細胞分化においてどのような役割を果たしているのかについては不明な点が多い。RAの病態において、GM-CSFが注目されている一方、GM-CSFはin vitroで破骨細胞分化を阻害することが報告されている。IL-4もまた破骨細胞分化を強力に阻害するが、破骨細胞前駆細胞の分化に関わっているという報告もある。今回の解析はそれらの臨床的な疑問点に一定の解答を提示する点で、学術的のみならず臨床的な意義も持っている。
|
