Cigarette Smoke Exposure Inhibits Osteoclast Apoptosis via the mtROS Pathway

It is widely known that smoking is a risk factor for bone loss and plays a key role in osteopenia. Despite this well-known association, the mechanisms by which smoking affects bone have not been definitively established. Since smoking increases bone loss and potentially affects bone resorption in response to mechanical force, we investigated the impact of cigarette smoke on osteoclast numbers and underlying mechanisms in a mouse model of orthodontic tooth movement (OTM). The experimental group was exposed to once-daily cigarette smoke while the control group was not, and tooth movement distance and osteoclast numbers were assessed. In addition, the effect of cigarette smoke extract (CSE) on osteoclast precursor proliferation and osteoclast apoptosis was assessed in vitro. We found that cigarette smoke exposure enhanced bone remodeling stimulated by mechanical force and increased osteoclast numbers in vivo. Also, CSE increased the number of osteoclasts by inhibiting osteoclast apoptosis via the mitochondrial reactive oxygen species/cytochrome C/caspase 3 pathway in vitro. Moreover, exposure of mice to cigarette smoke affected bone marrow cells, leading to increased formation of osteoclasts in vitro. This study identifies a previously unknown mechanism of how smoking has a detrimental impact on bone.

Zoledronic acid modulates osteoclast apoptosis through activation of the NF-κB signaling pathway in ovariectomized rats

Bone mass loss (osteoporosis) seen in postmenopausal women is an adverse factor for implant denture. Using an ovariectomized rat model, we studied the mechanism of estrogen-deficiency-caused bone loss and the therapeutic effect of Zoledronic acid. We observed that ovariectomized-caused resorption of bone tissue in the mandible was evident at four weeks and had not fully recovered by 12 weeks post-ovariectomized compared with the sham-operated controls. Further evaluation with a TUNEL assay showed ovariectomized enhanced apoptosis of osteoblasts but inhibited apoptosis of osteoclasts in the mandible. Zoledronic acid given subcutaneously as a single low dose was shown to counteract both of these ovariectomized effects. Immunohistochemical staining showed that ovariectomized induced the protein levels of RANKL and the 65-kD subunit of the NF-κB complex mainly in osteoclasts, as confirmed by staining for TRAP, a marker for osteoclasts, whereas zoledronic acid inhibited these inductions. Western blotting showed that the levels of RANKL, p65, as well as the phosphorylated form of p65, and IκB-α were all higher in the ovariectomized group than in the sham and ovariectomized + zoledronic acid groups at both the 4th- and 12th-week time points in the mandible. These data collectively suggest that ovariectomized causes bone mass loss by enhancing apoptosis of osteoblasts and inhibiting apoptosis of osteoclasts. In osteoclasts, these cellular effects may be achieved by activating RANKL-NF-κB signalling. Moreover, zoledronic acid elicits its therapeutic effects in the mandible by counteracting these cellular and molecular consequences of ovariectomized.

Synthesis and properties of Sr2+ doping α-tricalcium phosphate at low temperature

Strontium has been widely used in bone repair materials due to its roles in promoting osteoclast apoptosis and enhancing osteoblast proliferation. In this work, synthesis and the effects of Sr2+ doping α-tricalcium phosphate at low-temperature was studied. The setting time and the mechanical properties of α-tricalcium phosphate were controlled by varying the content of Sr2+. The synthesized compounds were evaluated by XRD, SEM, XPS, setting time, compressive strength, SBF immersion, and colorimetric CCK-8 assay. The results showed that Sr2+ can improve the compressive strength and cell activity of calcium phosphate bone cement.

The Use of Bisphosphonate-Hydroxyapatite Composite in Bone Augmentation

A good bone augmentation and regeneration depends essentially on the use of a high biomimetic hydroxyapatite, respectively of an osteoclast apoptosis promoting compound. The last one, used in oral or injectable form, leads to different gastrointestinal side effects. We suggested and studied, at non-clinical level, a composite of sodium alendronate linked on a biogene hydroxyapatite. The composite was obtained by putting an aqueous solution of alendronate into a suspension of hydroxyapatite in acetone. By physico-chemical methods the binding of alendronate (ALE) on hydroxyapatite was proved, the content of ALE in the composite being 22%. The patients can benefit from this composite due to a total elimination of gastrointestinal side effects as a consequence of limiting the bioactivity only locally.