Abstract

Osteoporosis, an imbalance in the bone-forming process mediated by osteoblasts and the bone-resorbing function mediated by osteoclasts, is a bone degenerative disease prevalent among the aged population. Due to deleterious side effects of currently available medications, probiotics as a potential treatment of osteoporosis is an appealing approach. Hence, this study aims to evaluate the beneficial effects of two novel Lactobacilli strain probiotics on bone health in ovariectomized (OVX) induced osteoporotic mice model and its underlying mechanisms. Forty-five 9-week-old Institute of Cancer Research (ICR) mice underwent either a sham-operation (n = 9) or OVX (n = 36). Four days after the operation, OVX mice were further divided into four groups and received either saline alone, Lactobacillus plantarum GKM3, Lactobacillus paracasei GKS6 or alendronate per day for 28 days. After sacrifice by decapitation, right distal femur diaphysis was imaged via micro-computed tomography (MCT) and parameters including bone volume/tissue volume ratio (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), and bone mineral density (BMD) were measured. Moreover, GKM3 and GKS6 on RANKL-induced osteoclast formation and osteoblast differentiation using in vitro cultures were also investigated. The results showed that both probiotics strains inhibited osteoporosis in the OVX mice model, with L. paracasei GKS6 outperforming L. plantarum GKM3. Besides this, both GKS6 and GKM3 promoted osteoblast differentiation and inhibited RANKL-induced osteoclast differentiation via the Bone Morphogenetic Proteins (BMP) and RANKL pathways, respectively. These findings suggested that both strains of Lactobacilli may be pursued as potential candidates for the treatment and management of osteoporosis, particularly in postmenopausal osteoporosis.

Highlights

  • Osteoporosis is a widespread bone disease that is most prevalent among older people and postmenopausal women

  • This study focuses on two particular novel strains of Lactobacilli, Lactobacillus plantarum strain GKM3 and Lactobacillus paracasei strain GKS6, to evaluate their functional effects on osteoporosis in OVX mice model when the two are prepared without soy skim milk

  • Lactobacillus plantarum GKM3 strain from fresh vegetable and Lactobacillus paracasei GKS6 strain from infant feces were isolated by Grape King Bio Ltd., Taoyuan, Taiwan and are respectively preserved at the Bioresource Collection and Research Center (BCRC) of the Food Industry Research and Development Institute (FIRDI) with the preservation numbers of BCRC 910,787 and BCRC 910788

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Summary

Introduction

Osteoporosis is a widespread bone disease that is most prevalent among older people and postmenopausal women. The occurrence of the disease is not limited to this demographic, it has become increasingly problematic following the increase in life expectancy and the aging populations of present-day society, contributing to increased medical cost and public concern [1,2]. Characteristics of osteoporosis include a decrease in bone mass and deterioration of bone tissue microarchitecture, leaving the patient susceptible to fracture due to bone fragility [2]. Once the balance is tipped in favor of increased osteoclastic resorption, as a result of menopausal estrogen deficiency in women, for example, the unbalanced rate of osteoblastic formation results in osteoporosis symptoms such as loss of bone mass and bone strength [3]. Therapies to promote osteoblast differentiation and inhibit osteoclast formation is an important therapeutic strategy

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