2. Academic Validation
  3. Dual Osteoprotective Actions of the Kefir Peptide KFP-1: Enhancement of Bone Formation and Suppression of Bone Resorption in Cells and Murine Models

Dual Osteoprotective Actions of the Kefir Peptide KFP-1: Enhancement of Bone Formation and Suppression of Bone Resorption in Cells and Murine Models

  • Calcif Tissue Int. 2026 Feb 17;117(1):32. doi: 10.1007/s00223-026-01487-w.
Min-Che Tung # 1 2,  Gary Ro-Lin Chang # 1,  Min-Yu Tu # 3 4,  Hueng-Chuen Fan 1 2,  Chih-Ching Yen 5,  Abdulkadir Cidem 1 6,  I-Chien Chen 1,  Chuan-Mu Chen 7 8 9
Affiliations

Affiliations

  • 1 Department of Life Sciences, Doctoral Program in Translational Medicine, National Chung Hsing University, Kuo Kuang Rd., Taichung, 402, Taiwan.
  • 2 Department of Surgery, and Department of Pediatrics, Tungs' Taichung Metro Harbor Hospital, Taichung, 435, Taiwan.
  • 3 Department of Orthopedic Surgery, Taichung Armed Forces General Hospital, Taichung, 411, Taiwan.
  • 4 Department of Health Business Administration, Meiho University, Pingtung, 912, Taiwan.
  • 5 Department of Internal Medicine, China Medical University Hospital, and China Medical University, Taichung, 404, Taiwan.
  • 6 Department of Molecular Biology and Genetics, Erzurum Technical University, 25250, Erzurum, Turkey.
  • 7 Department of Life Sciences, Doctoral Program in Translational Medicine, National Chung Hsing University, Kuo Kuang Rd., Taichung, 402, Taiwan. [email protected].
  • 8 The iEGG and Animal Biotechnology Center, and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, 402, Taiwan. [email protected].
  • 9 Center for General Educational, National Quemoy University, Kinmen, 892, Taiwan. [email protected].
  • # Contributed equally.
PMID: 41703166 DOI: 10.1007/s00223-026-01487-w
Abstract

KFP-1, a kefir-fermented peptide, promotes osteoblast differentiation and bone formation while inhibiting osteoclast differentiation and bone resorption. We also confirmed the bioaccessibility of KFP-1 in bone tissue and its overall benefits for bone health. Kefir is a dairy beverage rich in bioactive peptides with diverse health benefits. We identified a kefir-fermented peptide, KFP-1 (TEVPAINTIASAEPTVH), which enhances intestinal calcium absorption and may modulate bone remodeling. This study investigated the effects of KFP-1 on osteoblast and osteoclast gene expression and differentiation in BMMSCs, MC3T3-E1, BMMs, and Raw264.7 cells. Using iodine-125 labeling, we tracked KFP-1 distribution in mice following oral and intravenous administration, and evaluated its osteoprotective effects in AKR1A1 knockout (AKR1A1-KO) osteoporotic mice. KFP-1 upregulated osteogenic markers (ALP, Col1a1, OCN, OPG, RUNX2, OSX, BMP-2, β-catenin) and promoted osteoblast differentiation and mineralization, while downregulating osteoclastic markers (CTK, CTR, DC-STAMP, TRAP, c-Fos, c-Src, NFATc1) and inhibiting osteoclast differentiation and resorption via the inhibition of NFATc1, c-Fos, and c-Jun nuclear translocation and attenuation of RANKL-induced p38 MAPK, JNK, ERK, and NF-κB signaling. Biodistribution analysis showed KFP-1 reached femur and tibia at approximately 0.4% (oral) and 1% (intravenous) of the administered dose. In AKR1A1-KO mice, oral KFP-1 prevented bone loss, with additional calcium supplementation further improving cortical bone mechanical properties. These findings highlight KFP-1's dual action in promoting bone formation and inhibiting bone resorption, supporting its potential as a therapeutic Adjuvant or functional food ingredient for osteoporosis prevention and bone health.

Keywords

AKR1A1-KO osteoporotic mice; Biodistribution; KFP-1; Kefir peptides; Osteoblast; Osteoclast.

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