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Osteoporosis is a metabolic disease characterized by reduced osteoblast differentiation and proliferation. Oxidative stress plays a role in the pathogenesis of osteoporosis. Aucubin (AU), an iridoid glycoside, was previously shown to promote osteoblast differentiation. We investigated the effects of AU on MG63 human osteoblast-like cells treated with dexamethasone (Dex) or hydrogen peroxide (H 2 O 2 ) to induce oxidative damage. AU protected MG63 cells against apoptosis, and promoted increased expression of cytokines associated with osteoblast differentiation, including collagen I, osteocalcin (OCN), osteopontin (OPN), and osterix. In Dex- and H 2 O 2 -treated MG63 cells, AU also enhanced the expression of anti-oxidative stress-associated factors in the nuclear respiratory factor 2 signaling pathway, including superoxide dismutases 1 and 2, heme oxygenases 1 and 2, and catalase. In vivo , using a Dex-induced mouse model of osteoporosis, AU promoted increased cortical bone thickness, increased bone density, and tighter trabecular bone. Additionally, it stimulated an increase in the expression of collagen I, OCN, OPN, osterix, and phosphorylated Akt and Smads in bone tissue. Finally, AU stimulated the expression of cytokines associated with osteoblast differentiation in bone tissue and serum. Our data indicate AU may have therapeutic efficacy in osteoporosis.

Raloxifene is an antiresorptive drug, selective estrogen receptor modulator (SERM) used in the treatment of osteoporosis. Objective To evaluate proteins related to bone repair at the peri-implant bone in a rat model of osteoporosis treated with raloxifene. Material and Methods 72 rats were divided into three groups: SHAM (healthy animals), OVX (ovariectomized animals), and RLX (ovariectomized animals treated with raloxifene). Raloxifene was administered by gavage (1 mg/kg/day). Tibial implantation was performed 30 days after ovariectomy, and animals were euthanized at 14, 42, and 60 days postoperatively. Samples were collected and analyzed by immunohistochemical reactions, molecular analysis, and microtomographic parameters. Results RLX showed intense staining of all investigated proteins at both time points except for RUNX2. These results were similar to SHAM and opposite to OVX, showing mild staining. The PCR gene expression of OC and ALP values for RLX (P<0.05) followed by SHAM and OVX groups. For BSP data, the highest expression was observed in the RLX groups and the lowest expression was observed in the OVX groups (P<0.05). For RUNX2 data, RLX and SHAM groups showed greater values compared to OVX (P<0.05). At 60 days postoperatively, microtomography parameters, related to closed porosity, showed higher values for (Po.N), (Po.V), and (Po) in RLX and SHAM groups, whereas OVX groups showed lower results (P<0.05); (BV) values (P=0.009); regarding total porosity (Po.tot), RLX group had statistically significant lower values than OVX and SHAM groups (P=0.009). Regarding the open porosity (Po.V and Po), the SHAM group presented the highest values, followed by OVX and RLX groups (P<0.05). The Structural Model Index (SMI), RLX group showed a value closer to zero than SHAM group (P<0.05). Conclusions Raloxifene had a positive effect on the expression of osteoblastogenesis/mineralization-related proteins and on micro-CT parameters related to peri-implant bone healing.

Quercetin and rutin are common flavonoids in fruit and vegetables, and have been reported to affect bone development. However, the effect of flavonoids on osteoblast differentiation remains a matter of controversy. In the present study, mouse bone marrow mesenchymal stem cells (BMMSCs) were isolated and characterized for their use in osteoblast differentiation using two flavonoids, quercetin and rutin. BMMSCs were cultured in various concentrations of quercetin and rutin during the osteoblast differentiation period of 10 days. Both quercetin and rutin were found to up regulate the osteoblast differentiation in dose dependent manner, albeit to lesser extent in case of former than that of latter. Quercetin and rutin also increased alkaline phosphatase activity by about 150 and 240% and demonstrated mineralization up to 110 and 200% respectively as compared to control (which was considered as 100%). Further, both the flavonoids were also found to increase the expression of some of the prominent markers for differentiation of osteoblast like osteopontin, osterix, RunX2, osteoprotegerin and osteocalcin. The current data suggests that certain classes of flavonoids like rutin and quercetin can be used in the cure and management of osteodegenerative disorders due to their osteoblast specific differentiation activities., (Copyright © 2013 Elsevier GmbH. All rights reserved.)

Objective: Sodium butyrate (butyric acid; BA) is a major metabolic by-product of the anaerobic periodontopathic bacteria present in subgingival plaque. We examined the effects of BA and/or indomethacin on cell proliferation, the expression of cyclooxygenases (COXs), prostaglandin (PG) receptors (EP1-4), extracellular matrix proteins, such as type I collagen and osteopontin, and PGE(2) production, using ROS17/2.8 cells as osteoblasts., Methods: The rat clonal cell line ROS 17/2.8 was cultured with 0, 10(-5), 10(-4), and 10(-3)M BA in the presence or absence of 0.5 μM indomethacin, for up to 7 days. The expression of COX-1, COX-2, EP1, EP2, EP3, EP4, type I collagen, and osteopontin was examined at the mRNA and protein levels using real-time PCR and Western blotting, respectively. The amount of PGE(2) in the culture medium was measured by ELISA., Results: Proliferation of ROS 17/2.8 cells was not affected by the addition of BA. However, PGE(2) production and the expression of COX-1 and COX-2 increased with the addition of BA. In contrast, indomethacin, an inhibitor of COX, blocked the stimulatory effect of BA. Furthermore, EP2 expression increased with BA treatment, whereas EP1 expression was not affected and the expression of EP3 and EP4 was not detected. The addition of BA also increased the expression of type I collagen and osteopontin. Indomethacin blocked about 50% of the stimulatory effect of BA on type I collagen, whereas it did not block the effect on osteopontin., Conclusions: These results suggest that BA induces PGE(2) production by increasing the expression of COX-1 and COX-2 in osteoblasts, and that an autocrine action of the produced PGE(2), via EP1 or BA-induced EP2, is related to an increase in type I collagen expression by BA., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: The purpose of this study was to determine the effects of enamel matrix derivative on mRNA expression of markers related to periodontal healing., Study Design: Murine osteoprogenitor cells (MC3T3-E1) were grown for 12 and 16 days in mineralization media and stimulated with 100 microg/mL Emdogain (EMD). Cell cultures treated with 2% and 10% fetal calf serum (FCS) served as control. The mRNA expression of bone sialoprotein (BSP), osteopontin (OPN), and runt-related protein 2 (Runx2) was analyzed by real-time polymerase chain reaction. One-way analysis of variance was used for statistical analysis., Results: Stimulation with EMD significantly (P < .01) enhanced mRNA expression of BSP up to 13.9-fold and of OPN up to 3.2-fold at day 16 compared with the 2% FCS control. The expression of mRNA for transcription factor Runx2 was not significantly changed., Conclusion: The beneficial effects seen in periodontal regeneration after treatment with EMD may be related to an increase of the mineralization markers BSP and OPN at mRNA level.