The Role of Osteoclast Energy Metabolism in the Occurrence and Development of Osteoporosis

In recent decades, the mechanism underlying bone metabolic disorders based on energy metabolism has been heavily researched. Bone resorption by osteoclasts plays an important role in the occurrence and development of osteoporosis. However, the mechanism underlying the osteoclast energy metabolism disorder that interferes with bone homeostasis has not been determined. Bone resorption by osteoclasts is a process that consumes large amounts of adenosine triphosphate (ATP) produced by glycolysis and oxidative phosphorylation. In addition to glucose, fatty acids and amino acids can also be used as substrates to produce energy through oxidative phosphorylation. In this review, we summarize and analyze the energy-based phenotypic changes, epigenetic regulation, and coupling with systemic energy metabolism of osteoclasts during the development and progression of osteoporosis. At the same time, we propose a hypothesis, the compensatory recovery mechanism (involving the balance between osteoclast survival and functional activation), which may provide a new approach for the treatment of osteoporosis.

Osteogenic activity of lactoferrin and its application in contemporary dentistry

Introduction: Lactoferrin (Lf) is a protein in the transferrin family with many biological functions. One novel activity of lactoferrin described recently is its regulatory function in bone morphogenesis. Lactoferrin has been shown to promote the growth, development, and differentiation of osteoblasts as well as to decrease osteoclast survival. Lactoferrin receptors (LfRs) mediate the multiple functions of lactoferrin. This review focuses on LfRs associated with bone and the intestines. The best known LfR is small intestine LfR (intelectin), which facilitates iron absorption and iron metabolism in humans. Many data from in vitro and in vivo studies have indicated that lactoferrin promotes bone formation by increasing the proliferation of osteoblasts and the ability of cells to synthesize and mineralize the bone matrix. Lactoferrin additionally inhibits osteoclastogenesis, reducing the number of osteoclasts and thus bone resorption. Lactoferrin, with its numerous antimicrobial, anti-inflammatory, and also osteogenic properties has found a number of applications in contemporary dentistry, especially in dental surgery, in periodontology, and in pedodontics.Summary: This review presents in vivo and in vitro studies demonstrating the osteogenic and anti-inflammatory activity of Lf and its practical application in oral surgery and dentistry.

MicroRNA-29b Enhances Osteoclast Survival by Targeting BCL-2-Modifying Factor after Lipopolysaccharide Stimulation

Recent findings suggest that microRNAs (miRs) play a critical role in osteoclastogenesis, which regulates bone loss. We hypothesized that inflammation induces miR-29b, which increases the survival rate in osteoclasts (OCs), leading to bone loss. The expression level of miR-29b increased in OC stimulated by lipopolysaccharide (LPS) in an in vitro system which correlated with its increase in tibiae from mice that received LPS injections compared with those that received vehicle treatment. An miR-29b mimic increased OC survival rate without any change in OC differentiation, and furthermore, the inhibition of endogenous miR-29b induced by LPS decreased OC survival rate. Increased OC survival rate after overexpression of miR-29b was associated with antiapoptotic activity, as shown by staining annexin V-positive cells. We found that a target gene of miR-29b is BCL-2-modifying factor (Bmf), which acts as a proapoptotic factor, and that miR-29b binds to the 3′-UTR ofBmf. Our data demonstrate that LPS-induced miR-29b increases the number of OC by enhancing OC survival through decreased BMF.

Reactive oxygen species induce the association of SHP-1 with c-Src and the oxidation of both to enhance osteoclast survival

Loss of ovarian function causes oxidative stress as well as bone loss. We hypothesized that reactive oxygen species (ROS) induced by the failure of ovarian function are responsible for the bone loss by increasing the number of osteoclasts (OC). We found that ROS enhanced OC survival via Src homology 2 domain-containing phosphatase-1 (SHP-1), c-Src, Akt, and ERK. ROS induced the association of SHP-1 with c-Src as well as the oxidation of c-Src and SHP-1. This resulted in inactivation of SHP-1 and activation of c-Src via phosphorylation of Tyr416. Knockdown of c-Src or SHP-1 abolished the effect of ROS on OC survival. Moreover, downregulation of SHP-1 upregulated activation of c-Src, Akt, and ERK in the absence of any stimulus, suggesting that inactivation of SHP-1 is required for OC survival. We demonstrated that the association and oxidation of c-Src and SHP-1 by ROS are key steps in enhancing OC survival, which are responsible for increased bone loss when ovarian function ceases.