Table 1 Studies using KPs for osteoporosis prevention and treatment
From: Potential of Kefir-Derived Peptides, Probiotics, and Exopolysaccharides for Osteoporosis Management
Disease type | Experimental models & Intervention regimens (oral route) | Intervention outcomes |
|---|---|---|
Postmenopausal osteoporosis [8] | In vivo (OVX SD rats): 164, 328, and 656 mg KPs/kg BW/day for 12 weeks In vitro (Caco-2 cells): 400 μg/ml | 1. Serum:↓CTX 2. H&E (femur): ↓pathological score 3. μ-CT (femur): ↑BMD, ↑BV/TV, ↑Tb.N, ↑Tb.Th, ↓Tb.Sp 4. Nanoindentation (femoral cortical bone): ↑hardness, ↑elastic modulus 5. Caco-2 cells: ↑TRPV6-dependent Ca2+ influx |
Postmenopausal osteoporosis [15] | In vivo (OVX C57BL/6 J mice): 100 mg KPs/kg BW/day, or the combination of KPs and 10 mg CaCO3/kg BW/day for 8 weeks | 1. ↓Kidney-surrounding fat 2. μ-CT (femur): ↑BMD, ↑BV/TV, ↑Tb.N, ↓Tb.Sp 3. Nanoindentation (femoral cortical bone): ↑hardness, ↑elastic modulus, ↓residual indentation area 4. 16S rRNA analysis: KPs mildly modulate the structure of gut microbiota in OVX mice |
Osteoporosis [14] | Double-blinded human trial (n = 40): Control: CaCO3, 1500 mg/day Treatment: CaCO3 + KPs, 1600 mg/day, for 6 months | 1. Serum:↓β-CTX, ↑OC, ↑PTH 2. CT (hip): ↑BMD |
Vitamin C deficiency-induced osteoporosis [16] | In vivo (♂AKR1A1-KO mice): oral administration of 164 and 656 mg KPs/kg BW/day for 12 weeks In vitro (BMMs, BMMSCs): 0 ~ 20 μg/ml KPs | 1. Serum:↓ROS, ↓MDA, ↓IL-1β, ↓IL-6, ↓TNF-α, ↓CTX-1, ↓RANKL, ↑SOD, ↑catalase, ↑P1NP, ↑OC, ↑OPG 2. μ-CT (femur): ↑BMD, ↑BV/TV, ↑Tb.N, ↓Tb.Sp 3. Nanoindentation (femoral cortical bone): ↑hardness, ↑elastic modulus 4. OC differentiation: ↑ALP, ↑bone mineralization, ↑Collagen I, ↑β-catenin, ↑RUNX2, ↑BMP-2, ↑NFATc1, ↑HO-1, ↓p53 5. Osteoclast differentiation: ↓TRAP, ↓bone resorption, ↓c-Src, ↓cathepsin K, ↓NFATc1, ↓c-Fos 6. Intracellular signaling: ↓p38, ↓NF-κB, ↓Akt, ↓PLCγ2, ↓CREB-1 |
Hemophilia-induced osteoporosis [17] | In vivo (♂ Factor VIII-KO mice): oral administration of 164, 328, and 656 mg KPs/kg BW/day for 8 weeks In vitro (BMMs): 10, 20, and 40 μg/ml KPs | 1. Serum: ↓CTX-1, ↓RANKL, ↓IL-6, ↑OPG 2. H&E (femur): ↓pathological lesion, ↓TRAP 3. μ-CT (femur): ↑BMD, ↑BV/TV, ↑Tb.N, ↓Tb.Sp 4. μ-CT (lumbar): ↑Tb.N, ↓Tb.Sp 5. Nanoindentation (femoral cortical bone): ↑hardness, ↑elastic modulus 6. Osteoclast differentiation: ↓TRAP + osteoclasts |
Atherosclerosis-induced vascular calcification and osteoporosis [18] | In vivo (♂ ApoE-KO mice with a high-cholesterol diet): oral administration of 328 and 656 mg KPs/kg BW/day for 13 weeks | 1. Serum: ↓total cholesterol, ↓ox-LDL, ↓MDA, ↓TNF-α, ↓CTX-1, P1NP ↑ 2. Aortic arc (staining): ↓lipid, ↓collagen, ↓inflammation 3. Aortic arc (Western blot): ↓TNF-α, ↓IL-1β 4. μ-CT (femur): ↑BMD, ↑BV/TV, ↑Tb.N, ↑Tb.Th, ↓Tb.Sp, ↓SMI |
Femoral fracture [26] | In vivo (♂SD rats with femur-fracture surgery ): oral administration of 400 mg KPs/kg BW/day for 4 weeks In vitro (BMMSCs): 0 ~ 80 μg/ml KPs In vitro (MC3T3-E1): 400 μg/ml KPs | 1. Serum: ↑OC, ↑P1NP 2. X-ray (fracture site): fracture line completely vanished, full remodeling of cortex, ↑Lane & Sandhu score 3. Staining (fracture site): ↓cartilaginous callus, ↑calcified fibrocartilage 4. mRNA (fracture site): ↑Col1a1, ↑ALP, ↑SPP1, ↑VEGFA, ↑Cox-2 5. MC3T3-E1 cultures (mRNA): ↑Col1al, ↑ALP, ↑M-CSF, ↑Phospho1 6. BMMSC cultures: ↑bone mineralization |