Induction of apoptosis of human primary osteoclasts treated with extracts from the medicinal plant Emblica officinalis

<p>Abstract</p> <p>Background</p> <p>Osteoclasts (OCs) are involved in rheumatoid arthritis and in several pathologies associated with bone loss. Recent results support the concept that some medicinal plants and derived natural products are of great interest for developing therapeutic strategies against bone disorders, including rheumatoid arthritis and osteoporosis. In this study we determined whether extracts of <it>Emblica officinalis </it>fruits display activity of possible interest for the treatment of rheumatoid arthritis and osteoporosis by activating programmed cell death of human primary osteoclasts.</p> <p>Methods</p> <p>The effects of extracts from <it>Emblica officinalis </it>on differentiation and survival of human primary OCs cultures obtained from peripheral blood were determined by tartrate-acid resistant acid phosphatase (TRAP)-positivity and colorimetric MTT assay. The effects of <it>Emblica officinalis </it>extracts on induction of OCs apoptosis were studied using TUNEL and immunocytochemical analysis of FAS receptor expression. Finally, <it>in vitro </it>effects of <it>Emblica officinalis </it>extracts on NF-kB transcription factor activity were determined by gel shift experiments.</p> <p>Results</p> <p>Extracts of <it>Emblica officinalis </it>were able to induce programmed cell death of mature OCs, without altering, at the concentrations employed in our study, the process of osteoclastogenesis. <it>Emblica officinalis </it>increased the expression levels of Fas, a critical member of the apoptotic pathway. Gel shift experiments demonstrated that <it>Emblica officinalis </it>extracts act by interfering with NF-kB activity, a transcription factor involved in osteoclast biology. The data obtained demonstrate that <it>Emblica officinalis </it>extracts selectively compete with the binding of transcription factor NF-kB to its specific target DNA sequences. This effect might explain the observed effects of <it>Emblica officinalis </it>on the expression levels of interleukin-6, a NF-kB specific target gene.</p> <p>Conclusion</p> <p>Induction of apoptosis of osteoclasts could be an important strategy both in interfering with rheumatoid arthritis complications of the bone skeleton leading to joint destruction, and preventing and reducing osteoporosis. Accordingly, we suggest the application of <it>Emblica officinalis </it>extracts as an alternative tool for therapy applied to bone diseases.</p

Osteonecrosis of the Jaw—a Bone Site-Specific Effect of Bisphosphonates

A known complication that can occur in patients using bisphosphonates (BPs) is osteonecrosis of the jaw (ONJ). ONJ features bone exposure that may be associated with severe pain, swelling, local infection, and pathological fracture of the jaw. Current literature indicates that a complex combination of factors is necessary to induce ONJ. Several hypotheses about the pathophysiology of ONJ were previously reported. Here, we review these hypotheses and introduce new ideas and suggestions on this topic, focusing on bone site-specific cells, and the effect that BPs and other anti-resorptive drugs have on those cells. Gaining more insight into bone site-specific effects may help to better understand the pathogenesis ONJ, and contribute to the development of new bone site-specific anti-resorptive drugs

Surgical management of bisphosphonate-related osteonecrosis of the jaws: literature review

Surgical management of bisphosphonate-related osteonecrosis of the jaws (BRONJ) has been performed in an attempt to increase healing rates of the affected cases. This literature review aimed to identify clinical studies of surgical management of bisphosphonate-related osteonecrosis of the jaws (BRONJ) in order to assess their surgical treatment modalities, outcome and the follow-up. A search in the PubMed (Medline) database using specific terms and/or phrases as bisphosphonate-related osteonecrosis or jaw osteonecrosis, and surgical treatment or surgical management was conducted in order to identify clinical trials and cases of surgical treatment of BRONJ. The review search covered the time period from 2004 to 2014. All studies identified in the search were selected according to the inclusion criteria. Relevant information was recorded according to the following items: author, year, number of patients, BRONJ clinical stage, surgical treatment modality, clinical success, and follow-up. The initial database search yielded 345 titles. After filtering, 67 abstracts were selected culminating in 67 full text articles. A variety of surgical approach was found in this review: debridement, sequestrectomy bone resection, and bone reconstruction. Adjunctive therapies included hyperbaric oxygen, laser therapy, growth factors, and ozone. Although there are many indexed studies about BRONJ, well-documented reports concerning surgical therapeutically techniques are scarce, resulting from a lack of well-established protocols. Considerable differences were found regarding sample size, surgical treatment modalities and outcomes. Clinical studies with larger number of patients and longer follow-up are required to provide best information for each surgical treatment modality and its outcomes.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ Sagrado Coracao, Bauru, SP, BrazilUniv Sagrado Coracao, Dept Oral & Maxillofacial Surg, Rua Irma Arminda 10-50, BR-17011160 Bauru, SP, BrazilUniv Estadual Paulista, Fac Odontol, Aracatuba, SP, BrazilHosp Santa Catarina, Dept Stomatol, Sao Paulo, BrazilUniv Estadual Paulista, Fac Odontol, Aracatuba, SP, BrazilFAPESP: 2014/10693-