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ID PMID Title PublicationDate abstract
23253933 MicroRNA-146a in autoimmunity and innate immune responses. 2013 Apr MicroRNA (miRNA) are approximately 22 nucleotide single-stranded RNA that regulate the stability of target messenger RNA by selective binding to specific sites at the 3'-untranslated regions (UTR). This triggers repression in translation and mRNA degradation. It has been estimated that approximately 60% of all mRNA are under the control of miRNA. Among the known hundreds of miRNA, some are considered master regulators controlling either a single or multiple cellular pathways. Some miRNA are known to affect development and cell differentiation, while others are implicated in immunity and autoimmune diseases. A very interesting example is miR-146a, which has been reported to be downregulated in systemic lupus erythematosus and upregulated in rheumatoid arthritis (RA). Several groups have recently focused their attention on miRNA in the pathogenesis of RA. Interestingly, the expression of miR-146a is upregulated in different cell types and tissues in RA patients. miRNA in RA could also be considered as possible future targets for new therapeutic approaches. This discussion will focus on the current understanding in the function of miR-146a in endotoxin tolerance and cross-tolerance, and how it may contribute to modulate the overproduction of known pathogenic cytokines, such as tumour necrosis factor α.
23238772 Vitamin D in systemic and organ-specific autoimmune diseases. 2013 Oct Lately, vitamin D has been linked with metabolic and immunological processes, which established its role as an essential component of human health preservation. Vitamin D has been defined as natural immune modulators, and upon activation of its receptors (VDRs), it regulates calcium metabolism, cellular growth, proliferation and apoptosis, and other immunological functions. Epidemiological data underline a strong correlation between poor vitamin D status and higher risk for chronic inflammatory illnesses of various etiologies, including autoimmune diseases. Epidemiological, genetic, and basic studies indicated a potential role of vitamin D in the pathogenesis of certain systemic and organ-specific autoimmune diseases. These studies demonstrate correlation between low vitamin D and prevalence of diseases. In addition, VDRs' polymorphisms observed in some of these autoimmune diseases may further support a plausible pathogenic link. Notably, for some autoimmune disease, no correlation with vitamin D levels could be confirmed. Thus, in the current review we present the body of evidence regarding the plausible roles of vitamin D and VDR's polymorphism in the pathogenesis of autoimmunity. We summarize the data regarding systemic (i.e., systemic lupus erythematosus, rheumatoid arthritis, etc.) and organ-specific (i.e., multiple sclerosis, diabetes mellitus, primary biliary cirrhosis, etc.) autoimmune diseases, in which low level of vitamin D was found comparing to healthy subjects. In addition, we discuss the correlations between vitamin D levels and clinical manifestations and/or activity of diseases. In this context, we address the rational for vitamin D supplementation in patients suffering from autoimmune diseases. Further studies addressing the mechanisms by which vitamin D affects autoimmunity and the proper supplementation required are needed.
23229798 Pain and function in eight hundred and fifty nine patients comparing shoulder hemiprosthes 2013 Jan PURPOSE: Functional results of reversed total prostheses (RTP) have-to a very limited degree-been compared with those of other shoulder prosthesis types. The aim of our study was to compare results of four different types of shoulder prostheses in terms of function, pain, and quality of life (QoL). METHODS: Questionnaires were completed by 859 patients with shoulder prostheses registered in the Norwegian Arthroplasty Register. Patients with osteoarthritis (OA), rheumatoid arthritis (RA), or fracture sequela (FS) were included. Symptoms and function were assessed using the Oxford Shoulder Score (OSS, scale 0-48), and the EuroQoL-5D (EQ-5D) was used to assess QoL. RESULTS: Best functional results were obtained using conventional total prostheses (TPs) and RTPs -mean OSS improvement 18 and 16 units, respectively, vs 11 with hemiprostheses (HPs). For patients with OA, TPs performed best; for those with RA and FS, RTPs performed best; and those with HPs had the worst results in all diagnostic groups. The greatest improvement in QoL was seen in patients with TPs and RTPs. CONCLUSIONS: Conventional TPs provide the best improvement in pain, function and QoL in OA patients; RTPs are superior in patients with RA and FS.
23116308 Recent progress in studying curcumin and its nano-preparations for cancer therapy. 2013 A hydrophobic polyphenol compound extracted from turmeric, curcumin has been widely utilized as traditional medicines for centuries in China and India. Over the last decades, because of its low toxicity, extensive studies have been focused on its physicochemical properties and pharmacological activities on various diseases, such as cancer, cardio-vascular disease, inflammatory bowel, wound healing, Alzheimer's disease, rheumatoid arthritis, and diabetes. In particular, bioactivities of curcumin as an effective chemopreventive agent, chemo-/radio-sensitizer for tumor cells, and chemo-/radio-protector for normal organs, are of extraordinary research interests in the literature. Despite these advantages, applications of curcumin are limited in clinical trials because of its poor water solubility and low oral bioavailability. Nano-preparations as an emerging platform for the efficient delivery of anti-cancer drugs should overcome these problems. In this review, we at first briefly revisit important properties of curcumin as well as its uses in cancer treatments, and then overview various nano-preparations of curcumin for cancer therapy, including nanoparticles, liposomes, micelles, nanoemulsions, cyclodextrin complexes, nanodisks, nanofibres, solid lipid nanoparticles, and curcumin conjugates.
22451020 The effect of various disease-modifying anti-rheumatic drugs on the suppressive function o 2013 Feb Accumulating evidence suggests that defects in the function of CD4(+)CD25(+) regulatory T cells (Tregs) are important in immune-mediated diseases such as rheumatoid arthritis. Here, we investigated the effects of various disease-modifying anti-rheumatic drugs (DMARDs) on Treg function. Tregs and CD4(+)CD25(-) effector T cells (Teffs) were isolated from peripheral blood mononuclear cells obtained from healthy adults. Isolated Tregs were cultured with the DMARDs methotrexate (MTX), sulfasalazine (SSZ), leflunomide (LEF), or infliximab (INF). We found that each DMARD had a different effect on Treg function. SSZ and LEF inhibited the anti-proliferative function of Tregs on cocultured Teffs and reduced Treg expression of Foxp3 mRNA, whereas MTX and INF did not.
25594753 [The most common rheumatic diseases in patients with autoimmune liver disease in the Hospi 2014 Oct OBJECTIVE: To identify the most common autoimmune rheumatic diseases in patients with autoimmune liver disease in the Hospital Arzobispo Loayza (HAL) from 2008 -2013. MATERIALS AND METHODS: This is a transversal and descriptive study, we analyzed 125 medical records, only 86 patients fulfill the diagnostic criteria for autoimmune liver disease, of whom 46 had diagnosis of autoimmune hepatitis(AIH), 39 primary biliary cirrhosis(PBC) and just 1 primary sclerosing cholangitis (PSC). In our study group we looked for the clinical and laboratory characteristics most common and the frequency of cases in the HAL. RESULTS: Of the 46 patients with AIH, 16 (34.78%) were diagnosed with autoimmune rheumatic disease concurrence. Of these, 7 (15.22%) patients had Sjogren ́s Disease (SD), 6 (13.04%) had systemic lupus erythematosus (SLE) and 3 (6.52%) had rheumatoid arthritis (RA). We found 39 patients with PBC, 18 (46.15%) had other associated extrahepatic autoimmune disease, of whom 12 (30.77%) had SD, 3 (7.69%) SLE and 3 (7.69%) RA. One patient had the diagnosis of PSC, a sixty year old woman that had no concurrence with rheumatic disease. CONCLUSIONS: In our study was found that SD is the most common rheumatic disease in patients with AIH and PBC, followed by SLE and RA, with autoimmune liver disease with rheumatic symptoms and vice versa.
25556409 An observational study of alopecia areata in Sri Lankan adult patients. 2014 Dec OBJECTIVES: The objectives were to assess the demographical pattern, clinical presentation and therapeutic response in a cohort of patients with alopecia areata (AA) in Sri Lanka. METHODS: Hospital-based observational study of 290 adults aged 18 years or above. RESULTS: Alopecia areata was commoner in men (M:F=1.3:1). Age of onset was between 20-35 years (median 31 years) in 61%. Those with juvenile-onset AA (≤ 17 years, n=5) showed severe disease with many relapses and resistance to therapy. Late-onset AA (<50 years, n=12) was commoner among females and had mild disease activity. Alopecia areata was the commonest clinical type (93.7%), followed by alopecia universalis (n=10), ophiasis pattern (n=3), alopecia totalis (n=3), and reverse ophiasis pattern (n=1). Mild disease (>10% scalp area) was the commonest (82%). Alopecia was total, universal or extensive (>10% scalp area) in 18%. Sites involved were scalp (71%), beard only (20.5%) and multiple sites (8.7%). Nail changes were associated with severe disease. Associated autoimmune diseases were vitiligo 6 (2%), thyroid disease 5 (1.7%) and rheumatoid arthritis 1 (0.3%). Atopy (21%) was not associated with younger age of onset or severity of disease. Patients with a family history among first degree relatives had earlier onset of disease. Most (61%) were cured after 1-2 intralesional steroid injections. Oral dexamethasone mini pulse with or without topical 5% minoxidil lotion for 12 months or more were used in 28%. CONCLUSIONS: In Sri Lanka AA is a disease of the young. Extensive disease, juvenile onset, and associated nail changes were poor prognostic factors.
25378903 Surgical therapies for corneal perforations: 10 years of cases in a tertiary referral hosp 2014 PURPOSE: To report surgical therapies for corneal perforations in a tertiary referral hospital. METHODS: Thirty-one eyes of 31 patients (aged 62.4±18.3 years) with surgically treated corneal perforations from January 2002 to July 2013 were included in this study. Demographic data such as cause of corneal perforation, surgical procedures, and visual outcomes were retrospectively analyzed. RESULTS: The causes of corneal perforation (n=31) were divided into infectious (n=8, 26%) and noninfectious (n=23, 74%) categories. Infectious causes included fungal ulcer, herpetic stromal necrotizing keratitis, and bacterial ulcer. The causes of noninfectious keratopathy included corneal melting after removal of a metal foreign body, severe dry eye, lagophthalmos, canaliculitis, the oral anticancer drug S-1, keratoconus, rheumatoid arthritis, neurotrophic ulcer, atopic keratoconjunctivitis, and unknown causes. Initial surgical procedures included central large corneal graft (n=17), small corneal graft (n=7), and amniotic membrane transplantation (n=7). In two cases the perforation could not be sealed during the first surgical treatment and required subsequent procedures. All infectious keratitis required central large penetrating keratoplasty to obtain anatomical cure. In contrast, several surgical options were used for the treatment of noninfectious keratitis. After surgical treatment, anatomical cure was obtained in all cases. Mean postoperative best corrected visual acuity was better at 6 months (logMAR 1.3) than preoperatively (logMAR 1.8). CONCLUSION: Surgical therapies for corneal perforations in our hospital included central large lamellar/penetrating keratoplasty, small peripheral patch graft, and amniotic membrane transplantation. All treatments were effective. Corneal perforation due to the oral anticancer drug S-1 is newly reported.
25371696 Coadministration of Pinellia ternata Can Significantly Reduce Aconitum carmichaelii to Inh 2014 Chuanwu (CW), the mother root of Aconitum carmichaelii Debx., is a traditional Chinese medicine (TCM) for treating traumatic injuries, rheumatoid arthritis, and tumors. CW coadministered with banxia (BX), the root of Pinellia ternata, is also widely prescribed in clinical practice. However, the mechanism of this combination is yet deciphered. Current study aimed to investigate the effects of CW, including raw chuanwu (RCW) and processed chuanwu (PCW) alone, as well as CW coadministered with BX on CYP3A activity. Buspirone (BP) and testosterone (Tes) were used as specific probe substrates in vivo and ex vivo, respectively. CYP3A activity was determined by the metabolites formation ratios from the substrates. Compared with those in the control group, the metabolites formation ratios significantly decreased in the RCW and PCW alone groups, accompanied by a marked decrease in CYP3A protein and mRNA levels. However, there was a significant increase in those ratios in the RCW-BX and PCW-BX groups compared to the RCW and PCW alone groups. The results indicated that both RCW and PCW can inhibit CYP3A activity in rats because of downregulation of CYP3A protein and mRNA levels. Decreases in CYP3A activity can be reversed by coadministration with BX.
25222777 Predictors of atypical femoral fractures during long term bisphosphonate therapy: a case s 2014 Jul BACKGROUND & OBJECTIVES: Bisphosphonates (BPs) are the most widely prescribed medicines for the treatment of osteoporosis because of their efficacy and favourable safety profile. There have been, several reports on an increased incidence of atypical femoral fractures after long term treatment with BPs. The objective of this study was to evaluate the clinical presentation including prodromal symptoms, skeletal radiograph findings, type and duration of BPs received and treatment outcome of patients who developed atypical femoral fractures during bisphosphonate therapy. METHODS: In this retrospective study, eight patients with atypical femoral fractures were analysed based on clinical features, biochemical and radiological investigations. RESULTS: Of the eight patients, who sustained atypical femoral fractures, six were on alendronate and two were on zoledronate therapy before the fractures. In addition to BPs, two patients were on long term corticosteroid therapy for rheumatoid arthritis and Addison's disease. Three patients had bilateral atypical femoral fractures. Except one, all of them had prodromal symptoms prior to fracture. Skeletal radiograph showed cortical thickening, pointed (beaking of) cortical margin and transverse fracture in meta-diaphyseal location. Serum calcium, phosphate, alkaline phosphatase (ALP) and intact parathyroid hormone (iPTH) concentrations were within the reference range in all patients. INTERPRETATION & CONCLUSIONS: Long term bisphosphonate therapy may increase the risk of atypical femoral fractures. Presence of prodromal pain, thickened cortex with cortical beaking may be an early clue for predicting the atypical fractures. High risk patients need periodical skeletal survey and a close follow up for early detection of cases.
26786493 Pulmonary infection with caseating mediastinal lymphadenitis caused by Mycobacterium gordo 2014 Sep It is often difficult to discern true mycobacterial infection from colonization due to Mycobacterium gordonae (M. gordonae) since this organism is ubiquitous and is commonly an innocuous saprophyte. This study reports a rare case of caseating hilar adenopathy and pulmonary disease caused by M. gordonae in a patient with chronic obstructive pulmonary disease (COPD) and rheumatoid arthritis (RA) on maintenance steroids and methotrexate. Pathologic exam and cultures of lymph node excision biopsy and bronchoalveolar lavage (BAL) confirmed the diagnosis. Triple antimycobacterial therapy with azithromycin, ethambutol and rifabutin was administered. The patient had significant clinical and radiologic improvement and follow-up cultures confirmed microbiologic cure. Mycobacterium gordonae can be a rare cause of significant pulmonary infection, and positive sputum or BAL cultures for M. gordonae should not be automatically discarded and considered as nonpathogenic contaminants or colonizing organisms, especially in immunocompromised hosts with comorbidities. A detailed review of the case and relevant literature is provided.
25098768 Matrix metalloproteinase inhibitors: a patent review (2011 - 2013). 2014 Sep INTRODUCTION: The MMPs are involved in tissue remodeling. An imbalance between the inhibition and activation of MMPs results in excessive degradation of the extracellular matrix, which leads to some diseases including cancer, rheumatoid arthritis, osteoarthritis, heart disease and neurodegenerative diseases such as stroke. In this review, recent advances in the research of MMP inhibitors are reviewed. AREAS COVERED: This updated review summarized new patents on MMP inhibitors within January 2011 - December 2013. EXPERT OPINION: This review gives the latest development in the area of MMP inhibitors, which aim to treat disease processes associated with the MMPs. Structure-based design techniques have been used successfully in the search of selective MMP inhibitors, and these inhibitors can also be derived from natural products. Furthermore, imaging 'in vivo' technologies have been developed in order to follow the drug distribution to the targeted tissues, and to quantify the drug efficiency.
25076899 Xerophthalmia of Sjogren's Syndrome Diagnosed with Anti-Salivary Gland Protein 1 Antibodie 2014 May PURPOSE: The purpose of this report is to describe 2 patients with persistent severe dry eyes, positive Schirmer tests for Sjogren's syndrome (SS) but lacking antibodies to either Ro or La. These patients were diagnosed to have SS by detecting antibodies to salivary gland protein 1 (Sp1) and parotid secretory protein (PSP). This report emphasizes the existence of patients with SS who lack antibodies to either Ro or La and may therefore be misdiagnosed. Detection of novel autoantibodies, including antibodies to Sp1 and PSP, are helpful in identifying these patients. Initial presentation may simply be dry eyes. METHODS: Two patients who presented to our ophthalmology clinic are described. One of the patients underwent multiple procedures over a period of 10 years for severe xerophthalmia. The other patient had rheumatoid arthritis and xerophthalmia. However, in both patients, chronic xerophthalmia had been considered to be idiopathic because antibodies Ro and La were negative. Further serologic testing revealed antibodies to Sp1 and PSP. RESULTS: Two patients who lacked antibodies to Ro and La but not to Sp1 and PSP were diagnosed as having SS. CONCLUSION: Patients presenting with unexplained dry eyes may not always show the serology markers in the current criteria for SS, anti-Ro and anti-La. In these cases, investigation for novel, early antibodies to Sp1 and PSP is of importance in the diagnosis of SS.
25038679 Profiling of carotenoids and antioxidant capacity of microalgae from subtropical coastal a 2014 Dec 15 Carotenoids are associated with various health benefits, such as prevention of age-related macular degeneration, cataract, certain cancers, rheumatoid arthritis, muscular dystrophy and cardiovascular problems. As microalgae contain considerable amounts of carotenoids, there is a need to find species with high carotenoid content. Out of hundreds of Australian isolates, 12 microalgal species were screened for carotenoid profiles, carotenoid productivity, and in vitro antioxidant capacity (total phenolic content (TPC) and ORAC). The top four carotenoid producers at 4.68-6.88 mg/g dry weight (DW) were Dunaliella salina, Tetraselmis suecica, Isochrysis galbana, and Pavlova salina. TPC was low, with D. salina possessing the highest TPC (1.54 mg Gallic Acid Equivalents/g DW) and ORAC (577 μmol Trolox Equivalents/g DW). Results indicate that T. suecica, D. salina, P. salina and I. galbana could be further developed for commercial carotenoid production.
24967373 Human cytomegalovirus and autoimmune disease. 2014 Human cytomegalovirus (HCMV) represents a prototypic pathogenic member of the β-subgroup of the herpesvirus family. A range of HCMV features like its lytic replication in multiple tissues, the lifelong persistence through periods of latency and intermitting reactivation, the extraordinary large proteome, and extensive manipulation of adaptive and innate immunity make HCMV a high profile candidate for involvement in autoimmune disorders. We surveyed the available literature for reports on HCMV association with onset or exacerbation of autoimmune disease. A causative linkage between HCMV and systemic lupus erythematosus (SLE), systemic sclerosis (SSc), diabetes mellitus type 1, and rheumatoid arthritis (RA) is suggested by the literature. However, a clear association of HCMV seroprevalence and disease could not be established, leaving the question open whether HCMV could play a coresponsible role for onset of disease. For convincing conclusions population-based prospective studies must be performed in the future. Specific immunopathogenic mechanisms by which HCMV could contribute to the course of autoimmune disease have been suggested, for example, molecular mimicry by UL94 in SSc and UL83/pp65 in SLE patients, as well as aggravation of joint inflammation by induction and expansion of CD4+/CD28- T-cells in RA patients. Further studies are needed to validate these findings and to lay the grounds for targeted therapeutic intervention.
24953604 Fine characterization of glucosylated human IgG by biochemical and biophysical methods. 2014 Aug Nonenzymatic glycosylation of proteins finally generates advanced glycation end products (AGEs). The Schiff's base and Amadori adduct are stages of early glycation. AGE-modified IgG may undergo conformational alterations and the final entity of the process may be involved in the pathogenesis of Rheumatoid Arthritis (RA). In this study, glycation of human IgG was carried out with varying concentrations of glucose. Effect of incubation period on glycation of IgG has also been studied. Amadori adduct was detected by nitroblue tetrazolium (NBT) dye. The glucose mediated structural alterations in IgG were studied by UV, fluorescence, CD, FT-IR, DLS and DSC spectroscopy, and SDS-PAGE. Glycation-induced aggregation in AGE-IgG was reported in the form of binding of thioflavin T and congo red. Furthermore, AGE-modified IgG exhibited hyperchromicity, decrease of tryptophan fluorescence accompanied by increase in AGE specific fluorescence, loss of β-sheet, appearance of new peak in FT-IR, increase in hydrodynamic size and melting temperature. SDS-PAGE results showed decrease in the band intensity of glycosylated-IgG compared to native IgG. Glycation-induced modifications and aggregation of IgG might be important in the pathogenesis of RA.
24898449 Defining a pro-inflammatory neutrophil phenotype in response to schistosome eggs. 2014 Nov Neutrophils contribute to the pathological processes of a number of inflammatory disorders, including rheumatoid arthritis, sepsis and cystic fibrosis. Neutrophils also play prominent roles in schistosomiasis japonica liver fibrosis, being central mediators of inflammation following granuloma formation. In this study, we investigated the interaction between Schistosoma japonicum eggs and neutrophils, and the effect of eggs on the inflammatory phenotype of neutrophils. Our results showed significant upregulated expression of pro-inflammatory cytokines (IL-1α, IL-1β and IL-8) and chemokines (CCL3, CCL4 and CXCL2) in neutrophils after 4 h in vitro stimulation with S. japonicum eggs. Furthermore, mitochondrial DNA was released by stimulated neutrophils, and induced the production of matrix metalloproteinase 9 (MMP-9), a protease involved in inflammation and associated tissue destruction. We also found that intact live eggs and isolated soluble egg antigen (SEA) triggered the release of neutrophil extracellular traps (NETs), but, unlike those reported in bacterial or fungal infection, NETs did not kill schistosome eggs in vitro. Together these show that S. japonicum eggs can induce the inflammatory phenotype of neutrophils, and further our understanding of the host-parasite interplay that takes place within the in vivo microenvironment of schistosome-induced granuloma. These findings represent novel findings in a metazoan parasite, and confirm characteristics of NETs that have until now, only been observed in response to protozoan pathogens.
24840362 The clinical significance of posttranslational modification of autoantigens. 2014 Aug Posttranslational modifications (PTMs) are defined as covalent modifications occurring in a specific protein amino acid in a time- and signal-dependent manner. Under physiological conditions, proteins are posttranslationally modified to carry out a large number of cellular events from cell signaling to DNA replication. However, an absence, deficiency, or excess in PTMs of a given protein can evolve into a target to trigger autoimmunity, since PTMs arise in the periphery and may not occur in the thymus; hence, proteins with PTMs never tolerize developing thymocytes. Consequently, when PTMs arise during cellular responses, such as inflammation, these modified self-antigens can be taken up and processed by the antigen-presenting cells (APCs). Autoreactive T cells, which recognize peptides presented by APCs, can then infiltrate into host tissue where the modified antigen serves to amplify the autoimmune response, eventually leading to autoimmune pathology. Furthermore, a PTM occurring in an amino acid residue can induce changes in the net charge of the protein, leading to conformational modifications in the tertiary and quaternary structure of the protein, especially interaction with human leukocyte antigen (HLA) molecules. Molecular mimicry (MM) was until now the prevailing hypothesis explaining generation of autoimmunity; nevertheless, experimental animal models need inflammation via infection or other immunogens to ensure autoimmunity; MM alone is not sufficient to develop autoimmunity. PTMs could arise as an additive factor to MM, which is required to start an autoimmune response. PTMs have been found to be present in different pathologic conditions such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), antiphospholipid syndrome, and primary biliary cirrhosis. The aim of the present review is to expose protein posttranslational modifications and the evidence suggesting their role in the generation of autoimmunity.
24767185 Neutrophilic dermatoses as systemic diseases. 2014 May Neutrophilic dermatoses (ND) are inflammatory skin conditions characterized by a sterile infiltrate of normal polymorphonuclear leukocytes. The main clinical forms of ND include Sweet syndrome, pyoderma gangrenosum, erythema elevatum diutinum, subcorneal pustular dermatosis, and their atypical or transitional forms. ND are often idiopathic, but they may be associated with myeloid hematologic malignancies (Sweet syndrome), inflammatory bowel disease or rheumatoid arthritis (pyoderma gangrenosum), and monoclonal gammopathies (erythema elevatum diutinum, subcorneal pustular dermatosis). The possible infiltration of internal organs with neutrophils during the setting of ND underlies the concept of a neutrophilic systemic disease. ND may be seen as a polygenic autoinflammatory syndrome due to their frequent association with other autoinflammatory disorders (monogenic or polygenic) and the recent published efficacy of interleukin-1 blocking therapies in their management.
24704416 Bone defects: molecular and cellular therapeutic targets. 2014 Jun Bone defects are one of the most serious pathologies that need tissue regeneration therapies. Studies on mesenchymal stem cells are changing the way we treat bone diseases. MSCs have been used for the treatment of osteogenesis imperfecta, hypophosphatasia, osteonecrosis of the femoral head, osteoporosis, rheumatoid arthritis and osteoarthritis. In this context, it is becoming ever more clear that the future of therapies will be based on the use of stem cells. In this concise review, we highlight the importance of the use of MSCs in bone diseases, focusing on the role of histone deacetylases and Wnt pathways involved in osteogenesis. A better understanding of MSC biology and osteogenesis is needed in order to develop new and targeted therapeutic strategies for the treatment of bone diseases/disorders.