Award type：Award from Japanese society, conference, symposium, etc.  Country：Japan

Award type：Award from Japanese society, conference, symposium, etc.  Country：Japan

Language：English   Publisher：Biochemical and Biophysical Research Communications  

Systemic transplantation of mesenchymal stem cells (MSCs) and conditioned medium derived from MSCs have been reported to recover bone loss in animal models of osteoporosis; however, the underlying mechanisms remain unclear. We recently reported that extracellular vesicles released from human mesenchymal stem cells (hMSCs) prevent senescence of stem cells in bisphosphonate-related osteonecrosis of the jaw model. In this study, we aimed to compare the effects of conditioned medium (hMSCs-CM) from early and late passage hMSCs on cellular senescence and to verify the benefits of CM from early passage hMSCs in mitigating the progression of osteoporosis through the prevention of cellular senescence. We investigated the distinct endocrine effects of early (P5) and late (P17) passage hMSCs in vitro, as well as the preventive benefits of early passage hMSCs-CM in osteoporosis model triggered by ovariectomy. Our results indicate that long-term cultured hMSCs contributed to the progression of inflammatory transcriptional programs in P5 hMSCs, ultimately impairing their functionality and enhancing senescence-related characteristics. Conversely, early passage hMSCs reversed these alterations. Moreover, early passage hMSCs-CM infused intravenously in a postmenopausal osteoporosis mouse model suppressed bone degeneration and prevented osteoporosis by reducing ovariectomy-induced senescence in bone marrow MSCs and reducing the expression of senescence-associated secretory phenotype-related cytokines. Our findings highlight the high translational value of early passage hMSCs-CM in antiaging intervention and osteoporosis prevention.

DOI： 10.1016/j.bbrc.2024.149858

Web of Science

Scopus

PubMed

Language：English   Publisher：Scientific Reports  

Osteonecrosis of the femoral head (ONFH) is a type of ischemic osteonecrosis that causes pain, loss of function, and femoral head collapse. Here, we analyzed samples of femoral heads excised from patients with ONFH to clarify the relationship between ischemic osteonecrosis and cellular senescence. X-gal staining was strong and p16INK4a-positive cells were abundant in the transitional region of ONFH. The β-galactosidase-positive cells in the transitional region were also positive for nestin, periostin, or DMP-1. In contrast, no β-galactosidase-positive cells were detected in the healthy region. The senescence-associated p16INK4a, p21, and p53 were upregulated in ONFH tissue. We also examined and analyzed a mouse ischemic femoral osteonecrosis model in vivo to verify the association between ONFH and cellular senescence. Human mesenchymal stem cell-conditioned medium (MSC-CM) was administered to determine its therapeutic efficacy against cellular senescence and bone collapse. MSC-CM reduced the number of senescent cells and downregulated the aforementioned senescence-related genes. It also decreased the number of empty lacunae 4 weeks after ischemia induction and promoted bone formation. At 6 weeks post-surgery, MSC-CM increased the trabecular bone volume, thereby suppressing bone collapse. We conclude that cellular senescence is associated with ONFH and that MSC-CM suppresses bone collapse in this disorder.

DOI： 10.1038/s41598-024-53400-w

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.bbrc.2021.08.046

Authorship：Lead author   Language：English   Publishing type：Doctoral thesis  

DOI： 10.1177/0022034520906793

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1371/journal.pone.0208938

Language：English

DOI： 10.1007/978-1-0716-0655-1_9

Event date： 2024.7

Language：Japanese   Presentation type：Poster presentation  

Venue：東京   Country：Japan  

Event date： 2024.5

Language：Japanese   Presentation type：Poster presentation  

Venue：盛岡   Country：Japan  

Event date： 2023.11

Language：English   Presentation type：Poster presentation  

Country：Japan  

Event date： 2023.10

Language：Japanese   Presentation type：Poster presentation  

Venue：浜松   Country：Japan  

Event date： 2023.5

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：大阪   Country：Japan  

Application no：2023-022331  Date applied：2023.2