ArticleCalcified tissue international2026
Dual Osteoprotective Actions of the Kefir Peptide KFP-1: Enhancement of Bone Formation and Suppression of Bone Resorption in Cells and Murine Models.
Article in Calcified tissue international, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Not yet cited in PubMed.
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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.
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