In vertebrates, melatonin is primarily secreted from the pineal gland but it affects various biological processes including the sleep-wake cycle, vasomotor control, immune system and bone homeostasis. Melatonin has been known to promote osteoblast differentiation and bone maturation, but a direct role of melatonin on osteoclast differentiation is still elusive. The present study investigated the effect of melatonin on the differentiation of macrophages to osteoclasts. The presence of melatonin significantly reduced receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis and the siRNA-mediated knockdown of the melatonin receptor failed to overcome the anti-osteoclastogenic effect of melatonin. Although melatonin treatment did not affect the phosphorylation of extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinase (JNK), it markedly inhibited the activation of NF-κB and subsequent induction of nuclear factor of activated T cell cytoplasmic 1(NFATc1). Thus, our results suggest that melatonin could suppress osteoclast differentiation through downregulation of NF-κB pathway with concomitant decrease in the NFATc1 transcription factor induction. Furthermore, melatonin seems to have an anti-osteoclastogenic effect independent of plasma membrane melatonin receptors. In addition to previously reported properties of melatonin, our study proposes another aspect of melatonin and bone homeostasis.

The purpose of this study was to investigate the effects of mesoporous bioactive glass nanoparticle (MBN)/graphene oxide (GO) composites on the mineralization ability and differentiation potential of human dental pulp stem cells (hDPSCs). MBN/GO composites were synthesized using the sol-gel method and colloidal processing to enhance the bioactivity and mechanical properties of MBN. Characterization using FESEM, XRD, FTIR, and Raman spectrometry showed that the composites were successfully synthesized. hDPSCs were then cultured directly on the MBN/GO (40:1 and 20:1) composites in vitro. MBN/GO promoted the proliferation and alkaline phosphatase (ALP) activity of hDPSCs. In addition, qRT-PCR showed that MBN/GO regulated the mRNA levels of odontogenic markers (dentin sialophosphoprotein (DSPP), dentine matrix protein 1 (DMP-1), ALP, matrix extracellular phosphoglycoprotein (MEPE), bone morphogenetic protein 2 (BMP-2), and runt-related transcription factor 2 (RUNX-2)). The mRNA levels of DSPP and DMP-1, two odontogenesis-specific markers, were considerably upregulated in hDPSCs in response to growth on the MBN/GO composites. Western blot analysis revealed similar results. Alizarin red S staining was subsequently performed to further investigate MBN/GO-induced mineralization of hDPSCs. It was revealed that MBN/GO composites promote odontogenic differentiation via the Wnt/β-catenin signaling pathway. Collectively, the results of the present study suggest that MBN/GO composites may promote the differentiation of hDPSCs into odontoblast-like cells, and potentially induce dentin formation.

Bisphosphonates are one of the most widely used synthetic pyrophosphate analogues for the treatment of bone resorbing diseases such as osteoporosis, multiple myeloma, and bone metastases. Although the therapeutic usefulness of bisphosphonates mainly depends on their anti-osteoclastogenic effect, a severe side-effect of bisphosphonates called bisphosphonate-related osteonecrosis of the jaw (BRONJ) could not be explained by the anti-osteoclastogenic effect of bisphosphonates. In the present study, we have evaluated the changes in osteoclastogenesis- or osteoblastogenesis-supporting activities of osteocytes induced by bisphosphonates. Zoledronate, a nitrogen-containing bisphosphonate, markedly increased both the receptor activator of nuclear factor kB ligand (RANKL) as well as sclerostin in osteocyte-like MLO-Y4 cells, which were functionally revalidated by osteoclast/osteoblast generating activities of the conditioned medium obtained from zoledronate-treated MLO-Y4 cells. Of note, the zoledronate treatment-induced upregulation of the RANKL expression was mediated by autocrine interleukin-6 (IL-6) and subsequent activation of the signal transducer and activator of transcription 3 (STAT3) pathway. These results were evidenced by the blunted RANKL expression in the presence of a Janus activated kinase (JAK2)/STAT3 inhibitor, AG490. Also, the osteoclastogenesis-supporting activity was significantly decreased in zoledronate-treated MLO-Y4 cells in the presence of IL-6 neutralizing IgG compared to that of the control IgG. Thus, our results show previously unanticipated effects of anti-bone resorptive bisphosphonate and suggest a potential clinical importance of osteocytes in BRONJ development.

Dentin hypersensitivity (DH) is one of the most common clinical conditions usually associated with exposed dentinal surfaces. In this study, we identified the effectiveness of poly(amidoamine) (PAMAM) dendrimer-coated mesoporous bioactive glass nanoparticles (MBN) (PAMAM@MBN) on DH treatment, examining the ion-releasing effect, dentin remineralization, and the occluding effect of dentinal tubules. We synthesized MBN and PAMAM@MBN. After soaking each sample in simulated body fluid (SBF), we observed ion-releasing effects and dentin remineralization effects for 30 days. Also, we prepared 30 premolars to find the ratio of occluded dentinal tubules after applying MBN and PAMAM@MBN, respectively. The results showed that PAMAM did not disrupt the calcium ion-releasing ability or the dentin remineralization of MBN. The PAMAM@MBN showed a better occluding effect for dentinal tubules than that of MBN (p < 0.05). In terms of dentinal tubule occlusion, the gap between MBN was well occluded due to PAMAM. This implies that PAMAM@MBN could be effectively used in dentinal tubule sealing and remineralization.