Differential effects of antiepileptic drugs on human bone cells.

Antiepileptic drugs (AED) have been associated to in vivo deleterious consequences in bone tissue. The present work aimed to characterize the cellular and molecular effects of five different AED on human osteoclastogenesis and osteblastogenesis. It was observed that the different drugs had the ability to differentially modulate both processes, in a way dependent on the identity and dose of the AED. Shortly, valproic acid stimulated either osteoclastogenesis and osteoblastogenesis, whereas carbamazepine, gabapentin, and lamotrigine revealed an opposite behavior; topiramate elicited a decrease of osteoclast development and an increase in osteoblast differentiation. This is the first report describing the direct effects of different AED on human primary bone cells, which is a very important issue, because these drugs are usually consumed in long-term therapeutics, with acknowledged in vivo effects in bone tissue.

Complex osteoclastogenic inductive effects of nicotine over hydroxyapatite.

Cigarette smoke is associated to pathological weakening of bone tissue, being considered an important playmaker in conditions such as osteoporosis and periodontal bone loss. In addition, it is also associated with an increased risk of failure in bone regeneration strategies. The present work aimed to characterize the effects of nicotine on human osteoclastogenesis over a hydroxyapatite substrate. Osteoclast precursors were maintained in the absence or presence of the osteoclastogenesis enhancers M-CSF and RANKL, and were further treated with nicotine levels representative of the concentrations observed in the plasma and saliva of smokers. It was observed that nicotine at low concentrations elicit an increase in osteoclast differentiation, but only in the presence of M-CSF and RANKL it was also able to significantly increase the resorbing ability of osteoclasts. A slight downregulation of NFkB pathway and an increase in the production of TNF-α and, particularly PGE2, were involved in the observed effects of nicotine. At high concentrations, nicotine revealed cytotoxic effects, causing a decrease in cell density. In conclusion, nicotine at levels found in the plasma of the smokers, has the ability to act directly on osteoclast precursors, inducing its osteoclastogenic differentiation. The stimulatory behavior appears to be dependent on the stage of osteoclastic differentiation of the precursor cells, which means, in the absence of M-CSF and RANKL, it only favors the initial stages of osteoclast differentiation, while in the presence of the growth factors, a significant increase in their resorbing ability is also achieved.

Behaviour of co-cultured human osteoclastic and osteoblastic cells exposed to endodontic sealers' extracts.

OBJECTIVES: Bone tissue is constantly being moulded and shaped by the coordinated action of bone-resorbing osteoclasts and bone-synthesizing osteoblasts. This study addresses the long-term effects of endodontic sealers' extracts (AH Plus™, GuttaFlow™, Tubliseal™, Sealapex™ and RealSeal™) on co-cultures of human osteoclastic and osteoblastic cells. METHODS: The sealers were mixed according to the manufacturer's instructions, freshly extracted with culture medium (1.3 cm(2)/ml; 24 h; 37 °C, 5% CO2/air) and diluted (1:20-1:2,500). Co-cultures of osteoclastic and osteoblastic cells, established from precursors present in human peripheral blood mononuclear cells and bone marrow cells, respectively, were exposed to the extracts for 21 days. Co-cultures were characterized for the osteoclastic and osteoblastic response. RESULTS: The sealers caused a dose-dependent decrease on TRAP and ALP activities, respectively, an osteoclastic and an osteoblastic marker. The resorbing ability of the osteoclastic cells and the expression of osteoclastic and osteoblastic genes were also decreased; in addition, the extracts affected several intracellular signalling pathways. Inhibition was higher during the two first weeks, followed by adaptive cell responses. Osteoblastic response was more sensitive to the extracts' toxicity and showed lower adaptive ability. SIGNIFICANCE: A correlation to the clinical situation cannot be predicted; however, the results suggest that the sealers' eluents might disrupt the highly regulated interaction between osteoblastic and osteoclastic cells, compromising the local bone metabolism. Also, the higher susceptibility of the osteoblastic response might be particularly relevant in the initial stages of the healing of periapical lesions, due to the significant role of the bone formation events.

Exploring bioactive properties of marine cyanobacteria isolated from the Portuguese coast: high potential as a source of anticancer compounds.

The oceans remain a major source of natural compounds with potential in pharmacology. In particular, during the last few decades, marine cyanobacteria have been in focus as producers of interesting bioactive compounds, especially for the treatment of cancer. In this study, the anticancer potential of extracts from twenty eight marine cyanobacteria strains, belonging to the underexplored picoplanktonic genera, Cyanobium, Synechocystis and Synechococcus, and the filamentous genera, Nodosilinea, Leptolyngbya, Pseudanabaena and Romeria, were assessed in eight human tumor cell lines. First, a crude extract was obtained by dichloromethane:methanol extraction, and from it, three fractions were separated in a Si column chromatography. The crude extract and fractions were tested in eight human cancer cell lines for cell viability/toxicity, accessed with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactic dehydrogenase release (LDH) assays. Eight point nine percent of the strains revealed strong cytotoxicity; 17.8% showed moderate cytotoxicity, and 14.3% assays showed low toxicity. The results obtained revealed that the studied genera of marine cyanobacteria are a promising source of novel compounds with potential anticancer activity and highlight the interest in also exploring the smaller filamentous and picoplanktonic genera of cyanobacteria.

Variability of the paracrine-induced osteoclastogenesis by human breast cancer cell lines.

Breast cancer frequently metastasizes to the bone, often leading to the formation of osteolytic lesions. This work compares the paracrine-induced osteoclastogenesis mediated by four human breast cancer cell lines, the estrogen-receptor positive T47D and MCF-7 and the estrogen-negative SK-BR-3 and Hs-578T cell lines. Human osteoclast precursor cells were cultured in the presence of conditioned media from the breast cancer cell lines (10% and 20%), collected at different culture periods (48 h, 7 days, and 14 days). Cultures performed in the absence or the presence of M-CSF and RANKL served as negative and positive control, respectively. Results showed that the cell lines differentially expressed several osteoclastogenic genes. All cell lines exhibited a significant osteoclastogenic potential, evidenced by a high TRAP activity and number of osteoclastic cells, expression of several osteoclast-related genes, and, particularly, a high calcium phosphate resorption activity. Differences among the osteoclastogenic potential of the cell lines were noted. T47D and MCF-7 cell lines displayed the highest and the lowest osteoclastogenic response, respectively. Despite the variability observed, MEK and NF-κB signaling pathways, and, at a lesser extent, PGE2 production, seemed to have a central role on the observed osteoclastogenic response. In conclusion, the tested breast cancer cell lines exhibited a high osteoclastogenic potential, although with some variability on the cell response profile, a factor to be considered in the development of new therapeutic approaches for breast cancer-induced bone metastasis.

Marine cyanobacteria compounds with anticancer properties: a review on the implication of apoptosis.

Marine cyanobacteria have been considered a rich source of secondary metabolites with potential biotechnological applications, namely in the pharmacological field. Chemically diverse compounds were found to induce cytoxicity, anti-inflammatory and antibacterial activities. The potential of marine cyanobacteria as anticancer agents has however been the most explored and, besides cytotoxicity in tumor cell lines, several compounds have emerged as templates for the development of new anticancer drugs. The mechanisms implicated in the cytotoxicity of marine cyanobacteria compounds in tumor cell lines are still largely overlooked but several studies point to an implication in apoptosis. This association has been related to several apoptotic indicators such as cell cycle arrest, mitochondrial dysfunctions and oxidative damage, alterations in caspase cascade, alterations in specific proteins levels and alterations in the membrane sodium dynamics. In the present paper a compilation of the described marine cyanobacterial compounds with potential anticancer properties is presented and a review on the implication of apoptosis as the mechanism of cell death is discussed.

Reciprocal osteoblastic and osteoclastic modulation in co-cultured MG63 osteosarcoma cells and human osteoclast precursors.

Osteosarcoma is usually associated with a disturbed bone metabolism. The aim of this work was to characterize the reciprocal interactions between MG63 osteosarcoma cells and osteoclasts, in a co-culture system. Co-cultures were characterized throughout 21 days for the osteoclastogenic response and the expression of osteoblastic markers. Monocultures of MG63 cells and peripheral blood mononuclear cell (PBMC) and co-cultures of PBMC + human bone marrow cells (hBMC) were also performed. Compared to PBMC cultures, co-cultures yielded significantly increased gene expression of osteoclast-related markers, tartarate-acid resistant phosphatase (TRAP) activity, TRAP-positive multinucleated cells, cells with actin rings and vitronectin receptors (VNR) and calcitonin receptors (CTR) and calcium phosphate resorbing ability. Results showed that the development of functional osteoclasts required a very low number of MG63 cells, suggesting a high osteoclastogenic-triggering capacity of this cell line. Subjacent mechanisms involved the pathways MEK and NF-kB, although with a lower relevance than that observed on PBMC monocultures or co-cultures of hBMC + PBMC; PGE2 production also had a contribution. Compared to MG63 cell monocultures, the co-culture expressed lower levels of COL1 and ALP, and higher levels of BMP-2, suggesting that PBMC also modulated the osteoblastic behavior. While M-CSF appeared to be involved in the osteoclastogenic response on the MG63 + PBMC co-cultures, RANKL does not seem to be a key player in the process. On the other hand, sphingosine-1-phosphate production might contribute to the modulation of the osteoblastic behavior. Results suggest that the reciprocal modulation between osteosarcoma and osteoclastic cells might contribute to the disturbed bone metabolism associated with bone tumors.

Etidronate-based organic salts and ionic liquids: In vitro effects on bone metabolism.

Bisphosphonates are a class of drugs widely used for the treatment of several pathologies associated with increased bone resorption. Although displaying low oral bioavailability, these drugs have the ability to accumulate in bone matrix, where the biological effects are exerted. In the present work, four mono- and dianionic Etidronate-based Organic Salts and Ionic Liquids (Eti-OSILs) were developed by combination of this drug with the superbases 1,1,3,3-tetramethylguanidine (TMG) and 1,5-diazabicyclo(4.3.0)non-5-ene (DBN) as cations, aiming to improve not only the physicochemical properties of this seminal bisphosphonate, but also its efficacy in the modulation of cellular behavior, particularly on human osteoclasts and osteoblasts. It was observed that some of the developed compounds, in particular the dianionic ones, presented very high water solubility and diminished or absent polymorphism. Also, several of them appeared to be more cytotoxic against human breast and osteosarcoma cancer cell lines while retaining low toxicity to normal cells. Regarding bone cells, a promotion of an anabolic state was observed for all Eti-OSILs, primarily for the dianionic ones, which leads to an inhibition of osteoclastogenesis and an increase in osteoblastogenesis. The observed effects resulted from differential modulation of intracellular signaling pathways by the Eti-OSILs in comparison with Etidronate. Hence, these results pave the way for the development of more efficient and bioavailable ionic formulations of bisphosphonates aiming to effectively modulate bone metabolism, particularly in the case of increased bone resorption.

Characterisation of the osteoclastogenic potential of human osteoblastic and fibroblastic conditioned media.

Although M-CSF and RANKL are sufficient to promote in vitro osteoclastogenesis, in vivo this is a complex process which requires the action of many signalling molecules and cellular crosstalks. In this work, isolated or combined conditioned media, obtained from human adult skin fibroblast and bone marrow cells, were tested for their osteoclastogenic potential, through an indirect co-culture system, in the absence of recombinant M-CSF and RANKL. Osteoclastogenesis was assessed on human peripheral blood mononuclear cells (PBMC) and CD14+ cell cultures by quantification of total protein content, tartrate-resistant acid phosphatase (TRAP) activity, presence of multinucleated cells positive for TRAP, RT-PCR of TRAP, CATK, CA2, c-myc and c-src and presence of multinucleated cells displaying actin rings, vitronectin and calcitonin receptors. Cultures supplemented with M-CSF and RANKL were used as positive controls. It was observed that the conditioned medium from dexamethasone osteogenic-induced bone marrow cell cultures displayed the highest osteoclastogenic potential, with similar behaviour to that observed in the presence of both M-CSF and RANKL. Comparatively, fibroblastic conditioned medium elicited a slightly lower osteoclastogenic response. Combination of both conditioned media resulted in a significant increase of TRAP activity. On the other hand, conditioned medium from non-osteogenic-induced bone marrow cell cultures presented the lowest osteoclastogenic potential. These results were observed for both PBMC and CD14+ cell cultures, suggesting that fibroblast and osteoblast cells are able to modulate osteoclastogenesis in the absence of physical cell-cell interactions. In addition, osteoclastogenic potential of bone marrow cells increases with their osteoblastic differentiation.

Alendronic Acid as Ionic Liquid: New Perspective on Osteosarcoma.

Herein the quantitative synthesis of eight new mono- and dianionic Organic Salts and Ionic Liquids (OSILs) from alendronic acid (ALN) is reported by following two distinct sustainable and straightforward methodologies, according to the type of cation. The prepared ALN-OSILs were characterized by spectroscopic techniques and their solubility in water and biological fluids was determined. An evaluation of the toxicity towards human healthy cells and also human breast, lung and bone (osteosarcoma) cell lines was performed. Globally, it was observed that the monoanionic OSILs showed lower toxicity than the corresponding dianionic structures to all cell types. The highest cytotoxic effect was observed in OSILs containing a [C2OHMIM] cation, in particular [C2OHMIM][ALN]. The latter showed an improvement in IC50 values of ca. three orders of magnitude for the lung and bone cancer cell lines as well as fibroblasts in comparison with ALN. The development of OSILs with high cytotoxicity effect towards the tested cancer cell types, and containing an anti-resorbing molecule such as ALN may represent a promising strategy for the development of new pharmacological tools to be used in those pathological conditions.

Chemical composition, antioxidant, anti-inflammatory and antinociceptive activities of the ethanol extract of ripe fruits of Solanum lycocarpum St. Hil. (Solanaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Solanum lycocarpum St. Hil. (Solanaceae) is widely distributed in the Brazilian Cerrado and is used in folk medicine for treatment of inflammatory disorders, such as asthma and hepatitis, as weel as antirheumatic. AIM OF THE STUDY: The aims of this study were to evaluate the antioxidant, anti-inflammatory and antinociceptive activities of the ethanol extract (EE) obtained from the ripe fruits of S. lycocarpum and to identify its chemical constituents. MATERIALS AND METHODS: The extract was obtained by percolation with ethanol. This extract was analyzed by liquid chromatography coupled to a diode array detector and mass spectrometer (LC-DAD-MS) for identify its chemical constituents. The antioxidant activity was determined by the reaction with 1,1-diphenyl-2-picrylhydrazyl radical (DPPH). In vivo anti-inflammatory potential was assessed using carrageenan-induced paw edema model, while qualitative and quantitative histological analyses evaluated of the inflammatory infiltrate at different times and treatments. The antinociceptive effect of the EE was evaluated by acetic acid-induced abdominal writhing test, formalin-induced nociception and hot-plate test. RESULTS: The main compounds identified in EE were steroidal glycoalkaloids (such as robeneoside B or hydroxysolasonine isomers and solanandaine isomers), the aglycone alkaloids peiminine and solasodine, di- and tri-O-caffeoylquinic acid derivatives, O-coumaroyl caffeoylquinic acid derivatives, N1,N10-bis-(dihydrocaffeoyl)spermidine, di-O-hexoside, and hexonic acid. In addition, the EE showed significant antioxidant activity. Intraperitoneal (i.p.) treatment with EE (300 mg/kg) exhibited anti-inflammatory activity. Qualitative and quantitative histological analyses showed that EE significantly reduced the cell infiltrate in acute inflammation. The EE, in all doses evaluated, significantly reduced the abdominal contortions in mice. Besides, reduced licking time was found in both phases in the formalin test after treatment with EE (100 and 300 mg/kg). In addition, the opioid receptor antagonist naloxone reversed the antinociceptive activity of morphine in the both phases the test, but it did not reverse the antinociceptive activity of the EE. The EE (300 mg/kg) also caused an increase in the latency to response in the hot-plate test. CONCLUSION: The ripe fruits of S. lycocarpum exhibit antioxidant, anti-inflammatory, and antinociceptive activities, attributed mainly to the presence of alkaloids, such as solasodine and peiminine, as well as caffeoylquinic acids in their chemical composition. These results contribute to use of S. lycocarpum ripe fruits for the treatment of inflammatory and painful process.

Bisphosphonates and Cancer: A Relationship Beyond the Antiresorptive Effects.

Bisphosphonates (BPs) are stable analogues of the Inorganic Pyrophosphate (PPi), an endogenous regulator of bone mineralization, which can resist the hydrolysis in the gastrointestinal tract. Their conformation allows targeting the bone as a result of their three-dimensional structure, which makes them primary agents against osteoclast-mediated bone loss. They are used in many bone pathological conditions, like bone metastasis, because of its ability to modulate bone metabolism into a less favorable place to cancer cell growth, through the inhibition of osteoclastogenesis and bone resorption. This review is focused on the mechanisms of action through which BPs affect the cellular activity and survival, mainly on their antitumoral effects. In conclusion, BPs are considered the primary therapy for skeletal disorders due to its high affinity for bone, but now they are also considered as potential antitumor agents due to its ability to induce tumor cell apoptosis, inhibition of cell adhesion, invasion and proliferation, modulation of the immune system to target and eliminate cancer cells as well as affect the angiogenic mechanisms. Like any other drug, they also have some adverse effects, but the most common, the acute phase reaction, can be minimized with the intake of calcium and vitamin D.

Ionic Liquids for Topical Delivery in Cancer.

The unique properties of ionic liquids make them quite appealing for diverse applications, from "green" solvents (1st generation ionic liquids) to finely tuned materials (2nd generation ionic liquids). A decade ago, a 3rd generation of ionic liquids emerged which is focused on their prospective clinical applications, either as drugs per se or as adjuvants in drug formulations. In recent years, research focused on the use of ionic liquids for topical drug delivery has been increasing and holds great promise towards clinical application against skin cancers. This article highlights the growing relevance of ionic liquids in medicinal chemistry and pharmaceutical technology, which is opening new windows of opportunity.

A Novel Approach for Bisphosphonates: Ionic Liquids and Organic Salts from Zoledronic Acid.

Novel ionic liquids and organic salts based on mono- or dianionic zoledronate and protonated superbases, choline and n-alkylmethylimidazolium cations, were prepared and characterized by spectroscopic and thermal analyses. Most of the prepared salts display amorphous structures and very high solubility in water and saline solutions, especially the dianionic salts. Among the zoledronate-based ionic compounds, those containing choline [Ch] and methoxyethylmethylimidazolium [C3 OMIM] cations appear to have significant cytotoxicity against human osteosarcoma cells (MG63) and low toxicity toward healthy skin fibroblast cells. Because osteosarcoma is a bone pathology characterized by an increase in bone turnover rate, the results presented herein may be a promising starting point for the development of new ionic pharmaceutical drugs against osteosarcoma.

Functional characterization of two missense mutations in Pex5p - C11S and N526K.

Most newly synthesized peroxisomal proteins are targeted to the organelle by Pex5p, the peroxisomal cycling receptor. Pex5p interacts with these proteins in the cytosol, transports them to the peroxisomal docking/translocation machinery and promotes their translocation across the organelle membrane. Finally, Pex5p is recycled back to the cytosol in order to catalyse additional rounds of transportation. Although several properties of this protein sorting pathway have been recently uncovered, we are still far from comprehending many of its basic principles. Here, we describe the mechanistic implications of two single-amino acid substitutions in Pex5p. The first mutation characterized, Cys11Ser, blocks the recycling of Pex5p back into the cytosol at the step in which stage 2 Pex5p is converted into stage 3 Pex5p. The mutation Asn526Lys, previously described in a child with neonatal adrenoleukodystrophy and shown to abolish the PTS1-binding capacity of Pex5p, results in a Pex5p protein exhibiting import capacity. Protease assays suggest that the Asn526Lys mutation causes conformational alterations at the N-terminal half of Pex5p mimicking the ones induced by binding of a PTS1-containing peptide to the normal peroxin. The implications of these findings on the mechanism of protein translocation across the peroxisomal membrane are discussed.

Modulation of human osteoclastogenesis and osteoblastogenesis by lycopene.

Lycopene is a lipid-soluble pigment that is mainly found in tomato. It is the carotenoid that presents the highest antioxidant potential, and due to that, it has been implicated in a decrease of the risk of several oxidative-stress-related disorders, such as cancer, inflammatory diseases and osteoporosis. Nevertheless, at the present, there is no detailed information about how lycopene affects bone metabolism. The aim of the present work was to characterize the cellular and molecular effects of lycopene on human osteoclast and osteoblast differentiation and function. It was observed that lycopene, at levels found in plasma after the ingestion of lycopene-containing products, decreased osteoclast differentiation but did not affect cell density/survival; calcium-phosphate resorbing ability was also decreased. On the other hand, osteoblast proliferation (via a decrease on apoptosis) and differentiation were increased in the presence of lycopene. The observed effects in both cell types appeared to be related to significant changes in MEK signaling pathway, but also in protein kinase C pathway in osteoclasts and NFkB signaling in osteoblasts. In conclusion, lycopene appears to promote an anabolic state of bone metabolism, stimulating osteoblastogenesis and inhibiting osteoclastogenesis, which may contribute to the promotion of a proper health status of bone tissue. This information might be relevant for the prevention and delay in the progression of osteolytic bone conditions.

The N-terminal half of the peroxisomal cycling receptor Pex5p is a natively unfolded domain.

Targeting of most newly synthesised peroxisomal matrix proteins to the organelle requires Pex5p, the so-called PTS1 receptor. According to current models of peroxisomal biogenesis, Pex5p interacts with these proteins in the cytosol, transports them to the peroxisomal membrane and catalyses their translocation across the membrane. Presently, our knowledge on the structural details behind the interaction of Pex5p with the cargo proteins is reasonably complete. In contrast, information regarding the structure of the Pex5p N-terminal half (a region containing its peroxisomal targeting domain) is still limited. We have recently observed that the Stokes radius of this Pex5p domain is anomalously large, suggesting that this portion of the protein is either a structured elongated domain or that it adopts a low compactness conformation. Here, we address this issue using a combination of biophysical and biochemical approaches. Our results indicate that the N-terminal half of Pex5p is best described as a natively unfolded pre-molten globule-like domain. The implications of these findings on the mechanism of protein import into the peroxisome are discussed.

The Anticancer Potential of Ionic Liquids.

Among the many challenges that the pharmaceutical industry currently faces is the need to develop innovative and effective therapies. The investigation of alternative and effective therapies against cancer is a current goal of the pharmaceutical industry. Ionic liquids (ILs) have emerged recently as a topic of study by researchers in the pharmaceutical industry in their search for new therapeutic agents. By definition, ILs are organic salts with melting points below 100 °C that are composed only by ions. Their main advantage lies in the numerous possible combinations of cations and anions, which allow adjustments in their physicochemical properties. The combination between ILs and active pharmaceutical ingredients (APIs) may improve the properties of APIs. In addition, the antitumor properties of these compounds have been described. Several studies have reported the use of ILs in biomedical applications as therapeutic agents, namely as antitumor agents. This review describes the recent proposed applications of ILs as antitumor agents.

Testing the variability of PSA expression by different human prostate cancer cell lines by means of a new potentiometric device employing molecularly antibody assembled on graphene surface.

Prostate Specific Antigen (PSA) is widely used as a biomarker for prostate cancer. Recently, an electrochemical biosensor for PSA detection by means of molecularly imprinted polymers (MIPs) was developed. This work evaluated the performance and the effectiveness of that PSA biosensor in screening the biomarker PSA in biological media with complex composition, collected from different human prostate cell line cultures. For that, the prostate cancer LNCaP and PC3 cells, and the non-cancerous prostate cell line PNT2 were cultured for 2, 7 and 14days in either α-MEM or RPMI in the presence of 10% or 30% fetal bovine serum. Human gingival fibroblasts were used as a non-cancerous non-prostatic control. The different culture conditions modulated cellular proliferation and the expression of several prostate markers, including PSA. The electrochemical biosensor was able to specifically detect PSA in the culture media and values obtained were similar to those achieved by a commercial Enzyme-Linked Immunosorbent Assay (ELISA) kit, the most commonly used method for PSA quantification in prostate cancer diagnosis. Thus, the tested biosensor may represent a useful alternative as a diagnostic tool for PSA determination in biological samples.

Photomodulation of the osteoclastogenic potential of oral squamous carcinoma cells.

The treatment for oral cancer usually involves surgical excision followed by chemotherapy and/or radiotherapy. The combination of these therapies generally promotes a serious inflammation of the mucosa of the digestive tract, denominated mucositis, which compromises continuity of treatment. Photobiomodulation (PBM) therapy has been used successfully to reduce the oral mucositis, however there is still some controversy regarding the effects of this therapy on unintentionally irradiated tumor cells that may remain after cancer treatment. The aim of this study was to analyze the effect of PBM therapy (using parameters for mucositis) on the modulation of osteoclastogenic potential of a cell line derived from human lingual squamous cell carcinoma (SCC9). Previously irradiated SCC9 cells were co-cultured with human osteoclast precursors. Co-cultures performed with non-irradiated SCC9 cells served as control. After 7, 14 and 21 days the co-cultures were evaluated for the tartrate-resistant acid phosphatase (TRAP) activity, an osteoclastogenic marker. Additionally, the monocultures of SCC9 cells (non-irradiated and irradiated) were analyzed for cell viability/proliferation and for the expression of IL-11 and PTHrP. The irradiation of SCC9 cells with PBM with an energy density of 4 J/cm2 decreased the pro-osteoclastogenic potential of those cells. This may represent a potential useful side effect of PBM therapy. PBM (using recommended parameters for mucositis treatment) decreases the osteoclastogenic potential of oral squamous carcinoma cells.