Abstract
Chronic osteomyelitis, a bone infectious disease, is characterized by dysregulation of bone homeostasis, which results in excessive bone resorption. Lipopolysaccharide (LPS) which is a gram‐negative endotoxin was shown to inhibit osteoblast differentiation and to induce apoptosis and osteoclasts formation in vitro. While effective therapy against bacteria‐induced bone destruction is quite limited, the investigation of potential drugs that restore down‐regulated osteoblast function remains a major goal in the prevention of bone destruction in infective bone diseases. This investigation aimed to rescue LPS‐induced MC3T3‐E1 pre‐osteoblastic cell line using the methanolic extract of Cladophora glomerata enriched with Mn(II) ions by biosorption. LPS‐induced MC3T3‐E1 cultures supplemented with C. glomerata methanolic extract were tested for expression of the main genes and microRNAs involved in the osteogenesis pathway using RT‐PCR. Moreover, osteoclastogenesis of 4B12 cells was also investigated by tartrate‐resistant acid phosphatase (TRAP) assay. Treatment with algal extract significantly restored LPS‐suppressed bone mineralization and the mRNA expression levels of osteoblast‐specific genes such as runt‐related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and osteocalcin (OCN), osteopontin (OPN), miR‐27a and miR‐29b. The extract also inhibited osteoblast apoptosis, significantly restored the down‐regulated expression of Bcl‐2, and decreased the loss of MMP and reactive oxygen spices (ROS) production in MC3T3‐E1 cells induced by LPS. Furthermore, pre‐treatment with algal extract strongly decreased the activation of osteoclast in MC3T3‐E1‐4B12 coculture system stimulated by LPS. Our findings suggest that C. glomerata enriched with Mn(II) ions may be a potential raw material for the development of drug for preventing abnormal bone loss induced by LPS in bacteria‐induced bone osteomyelitis.
Highlights
Bone is considered as being a highly dynamic tissue undergoing continuous remodelling cycles, consisting of bone neoformation trough osteoblast differentiation and osteoclast-induced resorption
Bone replacement and neoformation basically respond to complex mechanisms that can be grouped into three main stages, with bone resorption initiation by osteoclasts, bone resorption transitioning to proper bone formation, and bone formation after osteoblasts differentiation
It has been proposed that released LPS from infected root canals could modulate the secretion of IL-1α and tumour necrosis factor-α (TNF-α) from macrophages, and stimulate metalloproteinase-1 (MMP-1) synthesis that will in turn initiate dramatic bone resorption.[7]
Summary
Bone is considered as being a highly dynamic tissue undergoing continuous remodelling cycles, consisting of bone neoformation trough osteoblast differentiation and osteoclast-induced resorption. Excessive pathological bone loss often occurs when an imbalance between formation and bone resorption appears, leading to the development of many severe inflammatory conditions such as osteomyelitis, bacterial arthritis and infected orthopaedic implants.[1,2]. Musculoskeletal infections, such as osteomyelitis, are among the most common and most challenging degenerative inflammatory diseases in clinical medicine. These are generally defined as an inflammatory process that could be limited to the bone and the joint, or can propagate to the bone marrow, the periosteum and the surrounding soft tissues, arising from the inoculation of one or more infectious organisms, and inducing significant destruction and necrosis of the local bone tissue, sequestrum formation and apposition of new bone tissue.[3,4]. The differentiation of osteoclasts takes place in several stages and is
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