Probiotic Propionibacterium freudenreichii MJ2 Enhances Osteoblast Differentiation and Mineralization by Increasing the OPG/RANKL Ratio

Abstract

Osteoblast differentiation is important for the development of bone and the maintenance of bone density. Propionibacterium freudenreichii is a probiotic with an anti-inflammatory property. The aim of this study was to investigate the enhancement effect of P. freudenreichii MJ2 (MJ2) isolated from raw milk on osteoblast differentiation, mineralization, and its signaling pathway. For in vitro and in vivo experiments, human fetal osteoblastic cell line hFOB 1.19 and an ovariectomized rat model were used, respectively. Expression levels of genes and proteins related to osteoblast differentiation and mineralization were measured by real-time polymerase chain reaction (qPCR) and Western blotting, respectively. Alizarin red S staining was performed to measure osteoblast mineralization. Heat-killed MJ2 (hkMJ2)-treated cells showed significantly increased osteoblast differentiation via an increase in the osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) ratio and significantly increased osteoblast mineralization by stimulating the expression of bone morphogenetic protein 2 and runt-related transcription factor 2. Additionally, oral administration of live or heat-killed MJ2 to ovariectomized rats inhibited osteoporosis-induced bone loss. Specifically, surface proteins isolated from MJ2 promoted osteoblast differentiation and mineralization. In conclusion, MJ2 enhanced osteoblast differentiation and mineralization through the OPG/RANKL signaling pathway and the effective component of MJ2 might be its surface proteins.

Propionibacterium freudenreichii Inhibits RANKL-Induced Osteoclast Differentiation and Ameliorates Rheumatoid Arthritis in Collagen-Induced Arthritis Mice

“…Meanwhile, the OPG/RANKL ratio, an indicator of inhibition of osteoclast differentiation, was significantly increased by MJ2 administration (Figure 7D). P. freudenreichii MJ2 reportedly increases osteoblast differentiation and BMD by enhancing the OPG/RANKL ratio [27]. In the present study, the OPG/RANKL ratio was significantly increased in MJ2 administered groups, which might contribute to an increase in BMD by inhibiting osteoclast differentiation.…”

“…L. rhamnosus prevents bone loss through inhibiting osteoclastogenesis in RANKL-induced osteoclast differentiation and through immunomodulation in ovariectomy mice [47]. P. freudenreichii MJ2 strain isolated from raw milk shows anti-inflammatory activity and improves bone health by promoting osteoblast differentiation [27]. In this study, we found that P. freudenreichii MJ2 inhibited osteoclast differentiation in RANKL-induced in vitro model.…”

“…Dairy Propionibacterium freudenreichii has been used as a cheese starter, and its probiotic and prebiotic properties have been revealed, including anti-inflammatory and bifidogenic activities [25,26]. Previously, we isolated a P. freudenreichii strain (designated as MJ2) from raw milk obtained from a local dairy farm and found that heat-killed P. freudenreichii promoted osteoblast differentiation and alleviated osteoporosis by increasing the OPG/RANKL ratio [27]. Therefore, based on our previous findings, we hypothesized that P. freudenreichii MJ2 could inhibit osteoclast differentiation, which contributes to the amelioration of RA.…”

Harness the functions of gut microbiome in tumorigenesis for cancer treatment

“…[ 115 , 116 , 117 ], Propionibacterium spp . [ 118 , 119 ], have potentials to be characterized as probiotics. Nonetheless, clinical trials are still required to examine the safety and effectiveness of probiotics for cancer therapy.…”

Probiyotiklerin Kültürde Mezenkimal Kök Hücre Davranışına Etkisi

“…Alizerin red boyaması ile mineralizasyonu artırdığı bulunmuştur. Overektomili sıçanlarda ağızdan MJ2 beslemesinin oluşan osteoporozu azalttığı bulunmuştur (19). Osteopozlu hastalardan alınan 25-OH vitamin D ve prokollajen tip 1 enterminal peptid örneklerinde Lactobacillus asidophilus ve ramnossus etkisi MC3T3-E1 ve osteoblastlar ve RAW 264.7 osteoklaslar etkisi incelendiğinde bütirik asit üzerinden osteoblastik olgunlaşmayı sağladıkları saptanmıştır.…”