In vitro and in vivo studies on exogenous polyamines and α-difluoromethylornithine to enhance bone formation and suppress osteoclast differentiation

Chien-Ching Lee ^1,2, Chia-Chun Chuang ^1,2, Chung-Hwan Chen ^3,4,5,6,7

¹Department of Anesthesia, An Nan Hospital, China Medical University, Tainan, 70965, Taiwan.
²Department of Medical Science Industries, Chang Jung Christian University, No.1, Changda Rd., Gueiren District, Tainan, 711301, Taiwan.
³Department of Orthopedics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, 80145, Taiwan.
⁴Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 80756, Taiwan.
⁵Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, 80756, Taiwan.
⁶Department of Orthopedics, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80756, Taiwan.
⁷Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, 80756, Taiwan.
⁸Department of Cosmetics and Fashion Styling, Cheng Shiu University, Kaohsiung, 83347, Taiwan.
⁹Department of Bioscience Technology, Chang Jung Christian University, Tainan, 711301, Taiwan.
¹⁰Department of Medical Science Industries, Chang Jung Christian University, No.1, Changda Rd., Gueiren District, Tainan, 711301, Taiwan. mjlee@mail.cjcu.edu.tw.
¹¹Department of Bioscience Technology, Chang Jung Christian University, Tainan, 711301, Taiwan. mjlee@mail.cjcu.edu.tw.

⁰Department of Anesthesia, An Nan Hospital, China Medical University, Tainan, 70965, Taiwan.

Amino Acids +

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June 27, 2024

View abstract on PubMed

Summary

Exogenous polyamines and DFMO stimulate bone formation by enhancing osteoblast activity and suppressing osteoclast function. This study shows their potential in treating osteoporosis and improving bone density in ovariectomized rats.

Area Of Science

Biochemistry
Cell Biology
Bone Biology

Background

Polyamines (putrescine, spermidine, spermine) and DFMO are known to influence bone metabolism.
Understanding their osteogenic potential is crucial for developing new osteoporosis treatments.

Purpose Of The Study

To investigate the osteogenic effects of exogenous polyamines and DFMO in vitro and in vivo.
To explore their impact on osteoblast differentiation and osteoclastogenesis.

Main Methods

In vitro studies on human osteoblasts (hOBs) and RAW 264.7 cells analyzed gene expression (Runx2, ALP, RANK, NFATc1), alkaline phosphatase (ALP) activity, tartrate-resistant acid phosphatase (TRAP) activity, and matrix mineralization.
In vivo studies utilized an ovariectomized rat model treated with polyamines and DFMO, with bone analysis via micro computed tomography (micro CT).

Main Results

Polyamines and DFMO significantly elevated mRNA levels of osteogenic genes (Runx2, ALP) and enhanced ALP activity and matrix mineralization in hOBs.
In RAW 264.7 cells, they reduced osteoclastogenic gene expression (RANK, NFATc1) and suppressed TRAP activity.
In ovariectomized rats, spermine (SPM) and DFMO improved bone volume and increased trabecular thickness.

Conclusions

Exogenous polyamines and DFMO demonstrate significant osteogenic potential in vitro and in vivo.
Their bone-forming effects may be linked to the suppression of osteoclastogenesis, offering a potential therapeutic strategy for bone loss conditions like osteoporosis.

Keywords:

Osteoclastogenic differentiation Osteogenic differentiation Osteoporosis Ovariectomized rat Polyamines α-difluoromethylornithine (DFMO)