Kefir peptides promote osteogenic differentiation to enhance bone fracture healing in rats

Jen-Chieh Lai; Hsin-Pei Li; Gary Ro-Lin Chang; Ying-Wei Lan; Yu-Hsuan Chen; Yan-Shen Tseng; Min-Yu Tu; Chien-Fu Chen; Hsiao-Ling Chen; Chuan-Mu Chen

doi:10.1016/j.lfs.2022.121090

Kefir peptides promote osteogenic differentiation to enhance bone fracture healing in rats

Life Sci. 2022 Dec 1:310:121090. doi: 10.1016/j.lfs.2022.121090. Epub 2022 Oct 17.

Authors

Affiliations

¹ Department of Life Sciences, Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan; Department of Orthopedic Surgery, Taichung Armed Forces General Hospital, Taichung 411, Taiwan; Graduated Department of Medicine, National Defense Medical Center, Taipei 114, Taiwan.
² Department of Life Sciences, Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan.
³ Department of Life Sciences, Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan; Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, OH, USA.
⁴ Department of Orthopedic Surgery, Taichung Armed Forces General Hospital, Taichung 411, Taiwan.
⁵ Aviation Physiology Research Laboratory, Kaohsiung Armed Forces General Hospital Gangshan Branch, Kaohsiung 820, Taiwan; Department of Health Business Administration, Meiho University, Pingtung 912, Taiwan.
⁶ Department of Life Sciences, Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan; Department of Orthopedic Surgery, Taichung Armed Forces General Hospital, Taichung 411, Taiwan.
⁷ Department of Biomedical Sciences, Da-Yeh University, Changhwa 515, Taiwan.
⁸ Department of Life Sciences, Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan; The iEGG and Animal Biotechnology Center, Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan. Electronic address: chchen1@dragon.nchu.edu.tw.

PMID: 36257457
DOI: 10.1016/j.lfs.2022.121090

Abstract

Aims: Fractures are the result of fragile bone structures after trauma caused by direct or indirect external impact or strong muscular contraction. Most fracture patients undergo surgical fixation to accelerate the healing process and restore the function of mutilated bone. Promoting the healing process remains an important issue for the treatment of bone fractures. Our previous studies demonstrated the remarkable bone-protective effects of kefir peptides (KPs) in ovariectomized rats and mice. In this study, we further evaluate the efficacy of KPs on fracture healing using a rat model of femoral fracture.

Main methods: Fifteen 8-week-old male Sprague Dawley (SD) rats were divided into the sham, mock, and KPs groups, in which the mock and the KPs groups underwent femur-fracture surgery with nail fixation, while the sham group underwent a sham operation. The next day, rats were orally administered with daily 400 mg/kg of KPs (KPs group) or distilled water (sham and mock groups) for four weeks. X-ray imaging, histochemical staining and serum osteogenic markers were applied for fracture healing evaluation. In vitro, mouse bone marrow mesenchymal stem cells (BMMSCs) and MC3T3-E1 line were subjected to osteoblast differentiation in the presence of KPs and compared with no KPs treatment.

Key findings: The results demonstrated that KPs treatment improved the progression of the fracture healing process (p < 0.05) and significantly increased the expressions of Col1a1, Alp, Spp1, Vegfa and Cox2 mRNA in the femurs of the KPs-treated fractured rats compared to those of the mock-treated fracture rats. In vitro, KPs treatment promoted bone regeneration factor (Col1a1, Alp, M-csf and Phospho1) expression in MC3T3-E1-derived osteoblast cultures (on Day 3) and enhanced osteogenic differentiation and mineralization in BMMSC-derived osteoblast cultures (on Day 17 and Day 21).

Significance: This is the first study to show that KPs can help with fracture healing by promoting osteogenic differentiation, and it also suggests that KPs can be used as a nutritional supplement to accelerate fracture healing.

Keywords: Femoral fracture; Fracture healing; Kefir peptides (KPs); Osteogenic differentiation.

MeSH terms

Animals
Cell Differentiation
Femoral Fractures* / drug therapy
Fracture Healing
Kefir*
Male
Mice
Osteogenesis
Peptides / pharmacology
Rats
Rats, Sprague-Dawley

Substances

Peptides