Research Paper Volume 12, Issue 20 pp 20753—20777

Substance P blocks ovariectomy-induced bone loss by modulating inflammation and potentiating stem cell function

Jiyuan Piao1, , Jeong Seop Park2, , Dae Yeon Hwang3, , Youngsook Son1,3, , Hyun Sook Hong2,3,4, ,

  • 1 Graduate School of Biotechnology and Department of Genetic Engineering, College of Life Science, Kyung Hee University, Seochun-dong, Kiheung-ku, Yong In, Republic of Korea
  • 2 Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul, Republic of Korea
  • 3 Kyung Hee Institute of Regenerative Medicine (KIRM), Medical Science Research Institute, Kyung Hee University Medical Center, Kyungheedae-ro, Dongdaemun-gu, Seoul, Republic of Korea
  • 4 East-West Medical Research Institute, Kyung Hee University Hospital, Kyungheedae-ro, Dongdaemun-gu, Seoul, Republic of Korea

Received: June 25, 2020       Accepted: August 1, 2020       Published: October 27, 2020
How to Cite

Copyright: © 2020 Piao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Osteoporosis is an age-related disease caused by imbalanced bone remodeling resulting from excessive bone resorption. Osteoporosis is tightly linked with induction of chronic inflammation, which activates osteoclasts and impairs osteoprogenitor in bone marrow. T helper 17 (Th17) cells have been recently recognized as one of major inducers in the pathophysiology of bone loss by secreting IL-17. Thus, modulation of Th17 development is anticipated to affect the progression of osteoporosis.

Substance P (SP) is reported to provide anti-inflammatory effects by controlling immune cell profile and also, promote restoration of damaged stem cell niches—the bone marrow—by repopulating BMSCs or potentiating its paracrine ability. This study aimed to explore the therapeutic effects of systemically injected SP on ovariectomy (OVX)-induced osteoporosis.

Resultantly, SP injection obviously blocked OVX-induced impairment of bone microarchitecture and reduction of the mineral density. In osteoporotic condition, SP could ameliorate chronic inflammation by promoting Treg cell polarization and inhibiting the development of osteoclastogenic Th17 cells. Moreover, SP could rejuvenate stem cell and enable stem cells to repopulate and differentiate into osteoblast.

Collectively, our study strongly suggests that SP treatment can block osteoporosis and furthermore, SP treatment provides therapeutic effect on chronic disease with inflammation and stem cell dysfunction.


CTX: collagen X; MLN: mesenteric lymph node; NK-1R: neurokinin-1 receptor; OCN: osteocalcin; OPG: osteoprotegerin; OVX: ovariectomy; SP: Substance P; TGF-β: transforming growth factor-beta; Th17: T helper 17; TNF-α: tumor necrosis factor- alpha; Treg: Regulatory T.