Treatment of Glenoid Wear with the Use of Augmented Glenoid Components in Total Shoulder Arthroplasty: A Scoping Review.

¼ Treatment of glenoid bone loss continues to be a challenge in total shoulder arthroplasty (TSA). Although correcting glenoid wear to patient's native anatomy is desirable in TSA, there is lack of consensus regarding how much glenoid wear correction is acceptable and necessary in both anatomic and reverse TSA.¼ Use of augmented glenoid components is a relatively new treatment strategy for addressing moderate-to-severe glenoid wear in TSA. Augmented glenoid components allow for predictable and easy correction of glenoid wear in the coronal and/or axial planes while at the same time maximizing implant seating, improving rotator cuff biomechanics, and preserving glenoid bone stock because of off-axis glenoid reaming.¼ Augmented glenoid components have distinct advantages over glenoid bone grafting. Glenoid bone grafting is technically demanding, adds to the surgical time, and carries a risk of nonunion and graft resorption with subsequent failure of the glenoid component.¼ The use of augmented glenoid components in TSA is steadily increasing with easy availability of computed tomography-based preoperative planning software and guidance technology (patient-specific instrumentation and computer navigation).¼ Although different augment designs (full wedge, half wedge, and step cut) are available and a particular design may provide advantages in specific glenoid wear patterns to minimize bone removal (i.e. a half wedge in B2 glenoids), there is no evidence to demonstrate the superiority of 1 design over others.

Extracorporeal shock wave therapy inhibits osteoclast differentiation by targeting NF-κB signaling pathway.

BACKGROUND: Extracorporeal shock wave therapy (ESWT) has been reported to promote osteoblast differentiation. However, the role of ESWT on osteoclast differentiation is still elusive. METHODS: This study analyzed the differentiation of osteoclasts in the shock wave group and the control group in vitro, and TRAP staining, RT-PCR, WB assays, and MTT assays were assessed between the two groups. Furthermore, we analyzed the bone formation in these two groups in vivo and micro-CT and trap staining were assessed between the two groups. RESULTS: We found that ESWT inhibited osteoclast maturation in vitro and ESW treatment of femur promoted bone formation in vivo. Mechanically, osteoclast differentiation was inhibited as the number of impulses increased and ESWT decreased endogenous levels of NTAFc1 and P65 protein. CONCLUSIONS: ESWT may be a potential therapy of osteoporosis through NF-κB signaling pathway.

Osteoporosis pathogenesis and treatment: existing and emerging avenues.

Osteoporotic fractures lead to increased disability and mortality in the elderly population. With the rapid increase in the aging population around the globe, more effective treatments for osteoporosis and osteoporotic fractures are urgently required. The underlying molecular mechanisms of osteoporosis are believed to be due to the increased activity of osteoclasts, decreased activity of osteoblasts, or both, which leads to an imbalance in the bone remodeling process with accelerated bone resorption and attenuated bone formation. Currently, the available clinical treatments for osteoporosis have mostly focused on factors influencing bone remodeling; however, they have their own limitations and side effects. Recently, cytokine immunotherapy, gene therapy, and stem cell therapy have become new approaches for the treatment of various diseases. This article reviews the latest research on bone remodeling mechanisms, as well as how this underpins current and potential novel treatments for osteoporosis.

Bioengineering the ameloblastoma tumour to study its effect on bone nodule formation.

Ameloblastoma is a benign, epithelial cancer of the jawbone, which causes bone resorption and disfigurement to patients affected. The interaction of ameloblastoma with its tumour stroma drives invasion and progression. We used stiff collagen matrices to engineer active bone forming stroma, to probe the interaction of ameloblastoma with its native tumour bone microenvironment. This bone-stroma was assessed by nano-CT, transmission electron microscopy (TEM), Raman spectroscopy and gene analysis. Furthermore, we investigated gene correlation between bone forming 3D bone stroma and ameloblastoma introduced 3D bone stroma. Ameloblastoma cells increased expression of MMP-2 and -9 and RANK temporally in 3D compared to 2D. Our 3D biomimetic model formed bone nodules of an average surface area of 0.1 mm2 and average height of 92.37 [Formula: see text] 7.96 µm over 21 days. We demonstrate a woven bone phenotype with distinct mineral and matrix components and increased expression of bone formation genes in our engineered bone. Introducing ameloblastoma to the bone stroma, completely inhibited bone formation, in a spatially specific manner. Multivariate gene analysis showed that ameloblastoma cells downregulate bone formation genes such as RUNX2. Through the development of a comprehensive bone stroma, we show that an ameloblastoma tumour mass prevents osteoblasts from forming new bone nodules and severely restricted the growth of existing bone nodules. We have identified potential pathways for this inhibition. More critically, we present novel findings on the interaction of stromal osteoblasts with ameloblastoma.

Effect of Vitamin E Supplement on Bone Turnover Markers in Postmenopausal Osteopenic Women: A Double-Blind, Randomized, Placebo-Controlled Trial.

Vitamin E is a strong anti-oxidative stress agent that affects the bone remodeling process. This study evaluates the effect of mixed-tocopherol supplements on bone remodeling in postmenopausal osteopenic women. A double-blinded, randomized, placebo-controlled trial study was designed to measure the effect of mixed-tocopherol on the bone turnover marker after 12 weeks of supplementation. All 52 osteopenic postmenopausal women were enrolled and allocated into two groups. The intervention group received mixed-tocopherol 400 IU/day, while the control group received placebo tablets. Fifty-two participants completed 12 weeks of follow-up. Under an intention-to-treat analysis, vitamin E produced a significant difference in the mean bone resorption marker (serum C-terminal telopeptide of type I collagen (CTX)) compared with the placebo group (-0.003 ± 0.09 and 0.121 ± 0.15, respectively (p < 0.001)). In the placebo group, the CTX had increased by 35.3% at 12 weeks of supplementation versus baseline (p < 0.001), while, in the vitamin E group, there was no significant change of bone resorption marker (p < 0.898). In conclusion, vitamin E (mixed-tocopherol) supplementation in postmenopausal osteopenic women may have a preventive effect on bone loss through anti-resorptive activity.

First Experimental Study of the Influence of Extracellular Vesicles Derived from Multipotent Stromal Cells on Osseointegration of Dental Implants.

Herein, the aim was to study the state of the bone tissue adjacent to dental implants after the use of extracellular vesicles derived from multipotent stromal cells (MSC EVs) of bone marrow origin in the experiment. In compliance with the rules of asepsis and antiseptics under general intravenous anesthesia with propofol, the screw dental implants were installed in the proximal condyles of the tibia of outbred rabbits without and with preliminary introduction of 19.2 µg MSC EVs into each bone tissue defect. In 3, 7, and 10 days after the operation, the density of bone tissue adjacent to different parts of the implant using an X-ray unit with densitometer was measured. In addition, the histological examinations of the bone site with the hole from the removed device and the soft tissues from the surface of the proximal tibial condyle in the area of intra-bone implants were made. It was found out that 3 days after implantation with the use of MSC EVs, the bone density was statistically significantly higher by 47.2% than after the same implantation, but without the injection of MSC EVs. It is possible that as a result of the immunomodulatory action of MSC EVs, the activity of inflammation decreases, and, respectively, the degree of vasodilation in bones and leukocyte infiltration of the soft tissues are lower, in comparison with the surgery performed in the control group. The bone fragments formed during implantation are mainly consolidated with each other and with the regenerating bone. Day 10 demonstrated that all animals with the use of MSC EVs had almost complete fusion of the screw device with the bone tissue, whereas after the operation without the application of MSC EVs, the heterogeneous histologic pattern was observed: From almost complete osseointegration of the implant to the absolute absence of contact between the foreign body and the new formed bone. Therefore, the use of MSC EVs during the introduction of dental implants into the proximal condyle of the tibia of rabbits contributes to an increase of the bone tissue density near the device after 3 days and to the achievement of consistently successful osseointegration of implants 10 days after the surgery.

Breast Cancer with Bone Metastasis: Molecular Insights and Clinical Management.

Despite the remarkable advances in the diagnosis and treatment of breast cancer patients, the presence or development of metastasis remains an incurable condition. Bone is one of the most frequent sites of distant dissemination and negatively impacts on patient's survival and overall frailty. The interplay between tumor cells and the bone microenvironment induces bone destruction and tumor progression. To date, the clinical management of bone metastatic breast cancer encompasses anti-tumor systemic therapies along with bone-targeting agents, aimed at slowing bone resorption to reduce the risk of skeletal-related events. However, their effect on patients' survival remains controversial. Unraveling the biology that governs the interplay between breast neoplastic cells and bone tissue would provide means for the development of new therapeutic agents. This article outlines the state-of-the art in the characterization and targeting the bone metastasis in breast cancer, focusing on the major clinical and translational studies on this clinically relevant topic.

Clostridium butyricum Alleviates Gut Microbiota Alteration-Induced Bone Loss after Bariatric Surgery by Promoting Bone Autophagy.

Bariatric surgery is the most common and effective treatment of severe obesity; however, these bariatric procedures always result in detrimental effects on bone metabolism by underlying mechanisms. This study aims to investigate the skeletal response to bariatric surgery and to explore whether Clostridium butyricum alleviates gut microbiota alteration-induced bone loss after bariatric surgery. Consequently, male SD rats received Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) surgery, respectively, followed by body weight recording. The bone loss after bariatric surgery was further determined by dual-energy X-ray absorptiometry (DXA), micro-CT measurement, histologic analyses, and Western blot. Besides, 16S rDNA gene sequencing was performed to determine the gut microbiota alteration after surgery, and intervention with fecal microbiota from RYGB donor was conducted in obese SD rats, followed by C. butyricum administration. Accordingly, rats in the RYGB and SG groups maintained sustained weight loss, and DXA and micro-CT measurement further demonstrated significant bone loss after bariatric surgery. Besides, histologic and Western blot analyses validated enhanced osteoclastogenesis and inhibited osteoblastogenesis and defective autophagy after surgery. The 16S rDNA gene sequencing suggested a significant alteration of gut microbiota composition in the RYGB group, and intervention with fecal microbiota from RYGB donor further determined that this kind of alteration contributed to the bone loss after RYGB. Meanwhile, C. butyricum might protect against this postoperative bone loss by promoting osteoblast autophagy. In summary, this study suggests novel mechanisms to clarify the skeletal response to bariatric surgery and provides a potential candidate for the treatment of bone disorder among bariatric patients. SIGNIFICANCE STATEMENT: The significance of this study is the discovery of obvious bone loss and defective autophagy after bariatric surgery. Besides, it is revealed that gut microbiota alterations could be the reason for impaired bone mass after bariatric surgery. Furthermore, Clostridium butyricum could alleviate the gut microbiota alteration-induced bone loss after bariatric surgery by promoting osteoblast autophagy.

Static magnetic field of 0.2-0.4 T promotes the recovery of hindlimb unloading-induced bone loss in mice.

PURPOSE: Bone loss is one of the most serious medical problem associated with prolonged weightlessness in long-term spaceflight mission. Skeletal reloading after prolonged spaceflight have indicated incomplete recovery of lost bone, which may lead to an increased risk of fractures in astronauts when returning to Earth. Substantial studies have revealed the capacity of static magnetic fields (SMFs) on treating various bone disorders, whereas it is unknown whether SMFs have the potential regulatory effects on bone quality in unloaded mice during unloading. This study was conducted to investigate the potential effects of whole-body SMF exposure with 0.2-0.4 T on the recovery of unloading-induced bone loss. MATERIALS AND METHODS: Eight-week-old male C57BL/6J mice were subjected to hindlimb unloading (HLU) for 4 weeks, following the mice were reloaded for 4 weeks under geomagnetic field (GMF) and SMF of 0.2-0.4 T. Bone quality indexes, including bone mineral density (BMD) and bone mineral content (BMC), bone microarchitecture, and bone mechanical properties were examined by the measurement of dual energy X-ray absorptiometry (DEXA), micro-computed tomography (Micro-CT), and 3-point bending. Bone turnover was evaluated by bone histomorphometric and serum biochemical assay. RESULTS: We found that SMF exposure for 4 weeks significantly promoted the recovery in HLU-induced decrease of BMD and BMC, deterioration of bone microarchitecture, and reduction of bone strength. The results from bone turnover determination revealed that SMF exposure for 4 weeks induced lower osteoclast number of trabecular bone and serum TRAP-5b levels in reloaded mice, whereas SMF showed no significant alteration in skeletal osteoblast number and serum osteocalcin levels. CONCLUSIONS: Together, our findings suggest that SMF of 0.2-0.4 T facilitated the recovery of unloading-induced bone loss by inhibiting the increase of bone resorption in reloaded mice, and indicate that SMF might become a promising biophysical countermeasure for maintaining bone health in astronauts after landing.

Intermittent Hypoxic Therapy Inhibits Allogenic Bone-Graft Resorption by Inhibition of Osteoclastogenesis in a Mouse Model.

Systemic Intermittent Hypoxic Therapy (IHT) relies on the adaptive response to hypoxic stress. We investigated allogenic bone-graft resorption in the lumbar spine in 48 mice. The mice were exposed to IHT for 1 week before surgery or 1 week after surgery and compared with controls after 1 and 4 weeks. Complete graft resorption was observed in 33-36% of the animals in the control group, but none in the preoperative IHT group. Increased bone-graft volume was demonstrated by micro-computed tomography in the preoperative IHT group after 1 week (p = 0.03) while a non-significant difference was observed after 4 weeks (p = 0.12). There were no significant differences in the postoperative IHT group. Increased concentration of immune cells was localized in the graft area, and more positive tartrate-resistant acid phosphatase (TRAP) staining was found in controls compared with IHT allogenic bone grafts. Systemic IHT resulted in a significant increase of the major osteoclast inhibitor osteoprotegerin as well as osteogenic and angiogenic regulators Tgfbr3, Fst3l, Wisp1, and Vegfd. Inflammatory cytokines and receptor activator of nuclear factor kappa-B ligand (RANKL) stimulators IL-6, IL-17a, IL-17f, and IL-23r increased after 1 and 4 weeks, and serum RANKL expression remained constant while Ccl3 and Ccl5 decreased. We conclude that the adaptive response to IHT activates numerous pathways leading to inhibition of osteoclastic activity and inhibition of allogenic bone-graft resorption.

Intrinsic Restriction of TNF-Mediated Inflammatory Osteoclastogenesis and Bone Resorption.

TNF (Tumor necrosis factor) is a pleiotropic cytokine that plays an important role in immunity and inflammatory bone destruction. Homeostatic osteoclastogenesis is effectively induced by RANKL (Receptor activator of nuclear factor kappa-B ligand). In contrast, TNF often acts on cell types other than osteoclasts, or synergically with RANKL to indirectly promote osteoclastogenesis and bone resorption. TNF and RANKL are members of the TNF superfamily. However, the direct osteoclastogenic capacity of TNF is much weaker than that of RANKL. Recent studies have uncovered key intrinsic mechanisms by which TNF acts on osteoclast precursors to restrain osteoclastogenesis, including the mechanisms mediated by RBP-J signaling, RBP-J and ITAM (Immunoreceptor tyrosine-based activation motif) crosstalk, RBP-J mediated regulatory network, NF-κB p100, IRF8, and Def6. Some of these mechanisms, such as RBP-J and its mediated regulatory network, uniquely and predominantly limit osteoclastogenesis mediated by TNF but not by RANKL. As a consequence, targeting RBP-J activities suppresses inflammatory bone destruction but does not significantly impact normal bone remodeling or inflammation. Hence, discovery of these intrinsic inhibitory mechanisms addresses why TNF has a weak osteoclastogenic potential, explains a significant difference between RANKL and TNF signaling, and provides potentially new or complementary therapeutic strategies to selectively treat inflammatory bone resorption, without undesirable effects on normal bone remodeling or immune response in disease settings.

Anti-CD20-Mediated B Cell Depletion Is Associated With Bone Preservation in Lymphoma Patients and Bone Mass Increase in Mice.

Immunotherapy with anti-CD20-specific antibodies (rituximab), has become the standard of care for B cell lymphoproliferative disorders and many autoimmune diseases. In rheumatological patients the effect of rituximab on bone mass yielded conflicting results, while in lymphoma patients it has not yet been described. Here, we used cross-sectional X-ray imaging (CT/PET-CT) to serially assess bone density in patients with follicular lymphoma receiving rituximab maintenance therapy. Remarkably, this treatment prevented the decline in bone mass observed in the control group of patients who did not receive active maintenance therapy. In accordance with these data, anti-CD20-mediated B cell depletion in normal C57BL/6J female mice led to a significant increase in bone mass, as reflected by a 7.7% increase in bone mineral density (whole femur), and a ~5% increase in cortical as well as trabecular tissue mineral density. Administration of anti-CD20 antibodies resulted in a significant decrease in osteoclastogenic signals, including RANKL, which correlated with a reduction in osteoclastogenic potential of bone marrow cells derived from B-cell-depleted animals. Taken together, our data suggest that in addition to its anti-tumor activity, anti-CD20 treatment has a favorable effect on bone mass. Our murine studies indicate that B cell depletion has a direct effect on bone remodeling.

Decision making in treatment after a first-time anterior glenohumeral dislocation: A Delphi approach by the Neer Circle of the American Shoulder and Elbow Surgeons.

BACKGROUND: The treatment of patients who sustain a first-time anterior glenohumeral dislocation (FTAGD) is controversial. The purpose of this study was to find consensus among experts using a validated iterative process in the treatment of patients after an FTAGD. METHODS: The Neer Circle is an organization of shoulder experts recognized for their service to the American Shoulder and Elbow Surgeons. Consensus among 72 identified experts from this group was sought with a series of surveys using the Delphi process. The first survey used open-ended questions designed to identify patient-related features that influence treatment decisions after an FTAGD. The second survey used a Likert scale to rank each feature's impact on treatment decisions. The third survey used highly impactful features to construct 162 clinical scenarios. For each scenario, experts recommended surgery or not and reported how strongly they made their recommendation. These data were analyzed to find clinical scenarios that had >90% consensus for recommending treatment. These data were also used in univariate and multivariate mixed-effects models to identify odds ratios (ORs) for different features and to assess how combining these features influenced the probability of surgery for specific populations. RESULTS: Of the 162 scenarios, 8 (5%) achieved >90% consensus for recommending surgery. All of these scenarios treated athletes with meaningful bone loss at the end of their season. In particular, for contact athletes aged > 14 years who were at the end of the season and had apprehension and meaningful bone loss, there was >90% consensus for recommending surgery after an FTAGD, with surgeons feeling very strongly about this recommendation. Of the scenarios, 22 (14%) reached >90% consensus for recommending nonoperative treatment. All of these scenarios lacked meaningful bone loss. In particular, surgeons felt very strongly about recommending nonoperative treatment after an FTAGD for non-athletes lacking apprehension without meaningful bone loss. The presence of meaningful bone loss (OR, 6.85; 95% confidence interval, 6.24-7.52) and apprehension (OR, 5.60; 95% confidence interval, 5.03-6.25) were the strongest predictors of surgery. When these 2 features were combined, profound effects increasing the probability of surgery for different populations (active-duty military, non-athletes, noncontact athletes, and contact athletes) were noted, particularly non-athletes. CONCLUSION: Consensus for recommending treatment of the FTAGD patient was not easily achieved. Certain combinations of patient-specific factors, such as the presence of meaningful bone loss and apprehension, increased the probability of surgery after an FTAGD in all populations. Over 90% of shoulder instability experts recommend surgery after an FTAGD for contact athletes aged > 14 years at the end of the season with both apprehension and meaningful bone loss. Over 90% of experts would not perform surgery after a first dislocation in patients who are not athletes and who lack apprehension without meaningful bone loss.

Exosomes derived from human exfoliated deciduous teeth ameliorate adult bone loss in mice through promoting osteogenesis.

Cell-free based therapy is an effective strategy in regenerative medicine as it avoids controversial issues, such as immunomodulation and stability. Recently, exosomes have been explored as a favorable substitution for stem cell therapy as they exhibit multiple advantages, such as the ability to be endocytosed and innate biocompatibility. This study aimed to investigate the effects of stem cells from human exfoliated deciduous teeth (SHED)-derived exosomes (SHED-Exo) on bone marrow stromal cells (BMSCs) osteogenesis and bone recovery. SHED-Exo were isolated, characterized, and applied to the bone loss area caused by periodontitis in a mouse model. We found that the injection of SHED-Exo restored bone loss to the same extent as original stem cells. Without affecting BMSCs proliferation, SHED-Exo mildly inhibited apoptosis. Moreover, SHED-Exo specifically promoted BMSCs osteogenesis and inhibited adipogenesis compared with SHED-derived conditioned medium. The expression of osteogenic marker genes, alkaline phosphatase activity, and Alizarin Red S staining of BMSCs was significantly increased by co-culturing with SHED-Exo. Moreover, Western blot analysis showed that Runx2, a key transcriptional factor in osteogenic differentiation, and p-Smad5 were upregulated upon SHED-Exo stimulation. Expression of the adipogenic marker PPARγ and the amount of lipid droplets decreased when exosomes were present. Low doses of exosomes inhibited the expression of the inflammatory cytokines IL-6 and TNF-α. In conclusion, SHED-Exo directly promoted BMSCs osteogenesis, differentiation, and bone formation. Therefore, exosomes have the potential to be utilized in the treatment of periodontitis and other bone diseases.

Osteoclast-derived apoptotic bodies show extended biological effects of parental cell in promoting bone defect healing.

Apoptotic bodies (ABs) traditionally considered as garbage bags that enclose residual components of dead cells are gaining increasing attentions due to their potential roles in intercellular communications. In bone turn over, at the end of bone resorption phase, most osteoclasts undergo apoptosis, generating large amounts of ABs. However, it remains unclear of the role of osteoclast-derived ABs in bone remodeling. Methods: Staurosporine (STS) was used to apoptotic induction and differential centrifugation was used to isolate ABs. Western blotting, flowcytometry and Transmission electron microscopy (TEM) were performed for ABs identification, while whole transcriptome of ABs from osteoclasts at different stages was detected by RNA-seq. VENN analysis and gene set enrichment analysis (GSEA) were performed to compare the profile similarities between ABs and parental cells. In vitro efficacy of ABs on angiogenesis and osteogenesis were evaluated by tube formation assay and ALP staining. In vivo, calvarial defect mice model was used to assess the effects of ABs-modified decalcified bone matrix (DBM) scaffolds on angiogenesis and osteogenesis. Results: Here we mapped the whole transcriptome paralleled with small RNA profiling of osteoclast derived ABs at distinct differentiation stages. Whole transcriptome analysis revealed significant differences in RNA signatures among the ABs generated from osteoclasts at different stages. By comparing with parental osteoclast RNA profiles, we found that the transcriptome of ABs exhibited high similarities with the corresponding parental cells. Functionally, in vitro and in vivo studies showed that similar with the parental cells, pOC-ABs potentiated endothelial progenitor cell proliferation and differentiation, whereas mOC-ABs promoted osteogenic differentiation. The inherited biological effects of ABs were shown mediated by several enriched lncRNAs of which the interference abolished AB functions. Conclusions: Our study revealed the total RNA profiles of osteoclast derived ABs and demonstrated their biological functions. Both gene set and functional analysis indicated that osteoclast derived ABs are biologically similar with the parental cells suggesting their bridging role in osteoclast-osteoblast coupling in bone remodeling.

Irradiation-induced senescence of bone marrow mesenchymal stem cells aggravates osteogenic differentiation dysfunction via paracrine signaling.

The role of cellular senescence induced by radiation in bone loss has attracted much attention. As one of the common complications of anticancer radiotherapy, irradiation-induced bone deterioration is common and clinically significant, but the pathological mechanism has not been elucidated. This study was performed to explore the cellular senescence and senescence-associated secretory phenotype (SASP) induction of bone marrow-derived mesenchymal stem cells (BMSCs) by irradiation and its role in osteogenic differentiation dysfunction. It was observed that irradiated BMSCs lost typical fibroblast-like morphology, exhibited suppressed viability and differentiation potential accompanied with senescence phenotypes, including an increase in senescence-associated ß-galactosidase (SA-ß-gal) staining-positive cells, and upregulated senescence-related genes p53/p21, whereas no changes happened to p16. Additionally, DNA damage γ-H2AX foci, G0/G1 phase of cell cycle arrest, and cellular and mitochondrial reactive oxygen species (ROS) increased in an irradiation dose-dependent manner. Meanwhile, the JAK1/STAT3 pathway was activated and accompanied by an increase in SASP secretion, such as IL-6, IL-8, and matrix metalloproteinase-9 (MMP9), whereas 0.8 µM JAK1 inhibitor (JAKi) treatment effectively inhibited the JAK pathway and SASP production. Furthermore, conditioned medium (CM) from irradiation-induced senescent (IRIS) BMSCs exhibited a markedly reduced ability in osteogenic differentiation and marker gene expression of osteoblasts, whereas CM with JAKi intervention may effectively improve these deterioration effects. In conclusion, irradiation could provoke BMSC senescence and SASP secretion and further aggravate osteogenic differentiation dysfunction via paracrine signaling, whereas SASP targeting may be a possible intervention strategy for alleviating irradiation-induced bone loss.

Micro-ARNs y células óseas / Micro RNAs and bone cells

Los micro-ARNs (miARNs) son pequeñas moléculas de ARN no codificante (de aproximadamente 15-25 nucleótidos), que regulan la expresión de genes involucrados en numerosas funciones biológicas, a través de la inhibición o degradación de un ARN mensajero diana. La homeostasis ósea se mantiene por el balance entre la formación osteoblástica y la resorción osteoclástica. La sobreexpresión o inhibición de miARNs específicos afecta la proliferación, diferenciación y actividad de osteoblastos, osteocitos y osteoclastos. Estas acciones son llevadas a cabo modulando la expresión de distintos factores transcripcionales y moléculas de señalización de las vías esenciales para la osteoblastogénesis u osteoclastogénesis. Estos efectos modifican el balance entre la formación y la resorción, determinando cambios en la homeostasis ósea. Esta revisión enumera una serie de miARNs que participan en la homeostasis ósea. Profundizando en el conocimiento de los mecanismos por medio de los cuales los miARNs actúan sobre el hueso, podrían revelarse nuevos usos potenciales futuros, entre los que se encuentran su utilidad como nuevos biomarcadores óseos o como agentes terapéuticos para el tratamiento de trastornos metabólicos óseos, pérdida de masa ósea o enfermedades óseas. (AU)

MicroRNAs (miRNAs) are endogenous small noncoding RNA molecules (of approximately 15­25 nucleotides), which regulate the expression of genes controlling numerous biological functions, through the inhibition or degradation of the target messenger RNA. Bone homeostasis is maintained by a balance between osteoblastic bone formation and osteoclastic bone resorption. The overexpression or inhibition of specific miRNAs affects cell proliferation, differentiation and activity of osteoblast, osteocytes and osteoclast. This action is done by modulating the expression of different transcription factors and signaling molecules of the most relevant pathways of osteoblastogenesis or osteoclastogenesis. This effect is able to modify the balance between bone formation and resorption, determining changes in bone homeostasis. The present review is an overview of a series of miRNAs involved in bone homeostasis. An in depth knowledge of the mechanisms by which miRNAs act on bone may reveal potential uses in the future as new bone biomarkers or therapeutic agents for treating metabolic bone disorders, bone loss and bone diseases. (AU)

Anterior open bite due to idiopathic condylar resorption during orthodontic retention of a Class II Division 1 malocclusion.

A common dilemma when treating anterior open bite is understanding its etiology. Idiopathic condylar resorption (ICR) can cause open bite in affected individuals. Although it is prudent to not treat patients with ICR until active resorption has ceased, orthodontists may begin treating them because anterior open bite from ICR may not appear before or during their orthodontic treatment. This article reports a 12-year-old female who was diagnosed with ICR 10 months after completion of her orthodontic treatment for a Class II Division 1 malocclusion. When a young patient with a high mandibular angle and previous skeletal or dental Class II malocclusion returns with an open bite during the retention phase, the patient's condyles must be carefully examined to determine whether any temporomandibular joint disorder, such as ICR, is present. Currently, the controversy over the cause and the cure for ICR is continuing to challenge orthodontists in diagnoses and treatments. Orthodontists should closely monitor and offer informed treatment options to patients with risk factors for ICR or signs of its pathology that might develop at any stage of orthodontic treatment, including the retention period.

Cartilage and Bone Destruction in Arthritis: Pathogenesis and Treatment Strategy: A Literature Review.

Arthritis is inflammation of the joints accompanied by osteochondral destruction. It can take many forms, including osteoarthritis, rheumatoid arthritis, and psoriatic arthritis. These diseases share one commonality-osteochondral destruction based on inflammation. The background includes a close interaction between osseous tissues and immune cells through various inflammatory cytokines. However, the tissues and cytokines that play major roles are different in each disease, and as a result, the mechanism of osteochondral destruction also differs. In recent years, there have been many findings regarding not only extracellular signaling pathways but also intracellular signaling pathways. In particular, we anticipate that the intracellular signals of osteoclasts, which play a central role in bone destruction, will become novel therapeutic targets. In this review, we have summarized the pathology of arthritis and the latest findings on the mechanism of osteochondral destruction, as well as present and future therapeutic strategies for these targets.

MicroRNA-92b-5p modulates melatonin-mediated osteogenic differentiation of bone marrow mesenchymal stem cells by targeting ICAM-1.

Osteoporosis is closely associated with the dysfunction of bone metabolism, which is caused by the imbalance between new bone formation and bone resorption. Osteogenic differentiation plays a vital role in maintaining the balance of bone microenvironment. The present study investigated whether melatonin participated in the osteogenic commitment of bone marrow mesenchymal stem cells (BMSCs) and further explored its underlying mechanisms. Our data showed that melatonin exhibited the capacity of regulating osteogenic differentiation of BMSCs, which was blocked by its membrane receptor inhibitor luzindole. Further study demonstrated that the expression of miR-92b-5p was up-regulated in BMSCs after administration of melatonin, and transfection of miR-92b-5p accelerated osteogenesis of BMSCs. In contrast, silence of miR-92b-5p inhibited the osteogenesis of BMSCs. The increase in osteoblast differentiation of BMSCs caused by melatonin was attenuated by miR-92b-5p AMO as well. Luciferase reporter assay, real-time qPCR analysis and western blot analysis confirmed that miR-92b-5p was involved in osteogenesis by directly targeting intracellular adhesion molecule-1 (ICAM-1). Melatonin improved the expression of miR-92b-5p, which could regulate the differentiation of BMSCs into osteoblasts by targeting ICAM-1. This study provided novel methods for treating osteoporosis.