Bone regeneration in osteoporosis: opportunities and challenges.

Bone regeneration is impaired in patients with osteoporosis. Previous studies have shown that periostin (Postn) shows great potential in bone regeneration treatments. However, the role of Postn in bone marrow mesenchymal stem cells (BMMSCs) remains to be elucidated. In this study, we isolated BMMSCs from ovariectomized rats (OVX-BMMSCs) and normal rats. Then, the expression levels of Postn and osteogenesis in OVX-BMMSCs were detected by alizarin red and alkaline phosphatase substrate staining, qPCR, and western blotting. We found that the levels of Postn in OVX-BMMSCs were significantly reduced. Furthermore, Postn overexpression in OVX-BMMSCs using recombinant lentivirus could improve the expression of alkaline phosphatase, runt-related transcription factor 2, and osteocalcin and reduce the expression of sclerostin. Besides, micro-computed tomography analysis, hematoxylin-eosin, and Masson's staining showed that the healing of the alveolar bone defect in osteoporotic rats could be promoted using Postn-modified OVX-BMMSC sheets. In conclusion, Postn-modified OVX-BMMSCs might restore the osteogenic capacity and promote alveolar bone regeneration, which may serve as a new therapeutic approach for bone regeneration in osteoporosis.

Potential Role of Pancreatic and Enteric Hormones in Regulating Bone Turnover

Alginate-hydrogel versus alginate-solid system. Efficacy in bone regeneration in osteoporosis.

Introduction : Osteoporosis stems from misbalance between bone forming and bone resorption, which lead to increased risks of bone fractures. In recent years, stem cell therapy introduced as a promising strategy for bone regeneration in osteoporosis due to their bone regeneration potential. However, stem cells require different stimulator to accelerate bone regeneration and repair processes. Previous Studies showed that Vitamin K2, as an osteoprotective factor, promote and inhibit proliferation and activity osteoblast and osteoclasts cell line, respectively. We aimed to elucidate effect vitamin K2 on dental pulp stem cells (DPSCs) proliferation and their differentiation into osteoblast, and evaluation effect of this vitamin on the process of differentiating peripheral blood mononuclear cells (PBMNCs) into osteoclast and the activity of these cells. Material and Methods: DPSCs and PBMNCs were used for induction towards the osteoblast and osteoclasts, respectively in the presence of various concentrations of vitamin K2. Cell viability was assessed by MTT assay. Osteogenesis assayed by alizarin red S staining and osteogenic gene expression as well as osteoclastogenesis by tartrate-resistant acid phosphatase (TRAP) staining, Annexin V/PI assay, pit formation and NF-κB gene expression. Results: Our data showed that vitamin K2 at a concentration of 10µM increased both proliferation and osteogenesis activities of DPSCs and also increased the incidence of apoptosis in TRAP-positive cells as well as decrees in an expression of NF-κB and pit formation. Conclusion: These results suggest that simultaneous use of vitamin K2 and DPSCs can be a purpose of stem cell therapy in osteoporosis and conducting further pre-clinical studies.

Osteoporosis (OP) is defined by bone mass loss and structural bone deterioration. Currently, there are no effective therapies for OP treatment. Circular RNAs (circRNAs) have been reported to have an important function in stem cell osteogenesis and to be associated with OP. Most circRNA roles in OP remain unclear. In the present study, we employed circRNA microarray to investigate circRNA expression patterns in OP and non‐OP patient bone tissues. The circRNA‐miRNA‐mRNA interaction was predicted using bioinformatic analysis and confirmed by RNA FISH, RIP and dual‐luciferase reporter assays. ARS and ALP staining was used to detect the degree of osteogenic differentiation in human adipose‐derived mesenchymal stem cells (hASCs) in vitro. In vivo osteogenesis in hASCs encapsulated in collagen‐based hydrogels was tested with heterotopic bone formation assay in nude mice. Our research found that circFOXP1 was significantly down‐regulated in OP patient bone tissues and functioned like a miRNA sponge targeting miR‐33a‐5p to increase FOXP1 expression. In vivo and in vitro analyses showed that circFOXP1 enhances hASC osteogenesis by sponging miR‐33a‐5p. Conversely, miR‐33a‐5p inhibits osteogenesis by targeting FOXP1 3′‐UTR and down‐regulating FOXP1 expression. These results determined that circFOXP1 binding to miR‐33a‐5p promotes hASC osteogenic differentiation by targeting FOXP1. Therefore, circFOXP7ay prevent OP and can be used as a candidate OP therapeutic target.

The clinical condition involving dental implants, characterized by soft tissue inflammation, bleeding, suppuration and rapid bone loss is widely known as peri implantitis. The main objective in the treatment of peri-implantis is to arrest the progression of the disease and at the same time to keep the dental implant in the mouth solving the inflammations signs of bleeding and pain. The aim of this paper is to highlight the effectiveness of the use of titanium brush and antimicrobial photodynamic therapy (aPDT) to decontaminate the implant surface, in association with regenerative procedures by means of autologous bone and demineralized bovine bone mineral (DBBM) in the treatment of peri-implantitis defects.

We evaluated the bone regeneration and healing effect of Medicarpin (med) in cortical bone defect model that heals by intramembranous ossification. For the study, female Sprague–Dawley rats were ovariectomized and rendered osteopenic. A drill hole injury was generated in mid femoral bones of all the animals. Med treatment was commenced the day after and continued for 15 days. PTH was taken as a reference standard. Fifteen days post-treatment, animals were sacrificed. Bones were collected for histomorphometry studies at the injury site by micro-computed tomography (μCT) and confocal microscopy. RNA and protein was harvested from newly generated bone. For immunohistochemistry, 5μm sections of decalcified femur bone adjoining the drill hole site were cut. By μCT analysis and calcein labeling of newly generated bone it was found that med promotes bone healing and new bone formation at the injury site and was comparable to PTH in many aspects. Med treatment led to increase in the Runx-2 and osteocalcin signals indicating expansion of osteoprogenitors at the injury site as evaluated by qPCR and immunohistochemical localization. It was observed that med promoted bone regeneration by activating canonical Wnt and notch signaling pathway. This was evident by increased transcript and protein levels of Wnt and notch signaling components in the defect region. Finally, we confirmed that med treatment leads to elevated bone healing in pre-osteoblasts by co localization of beta catenin with osteoblast marker alkaline phosphatase. In conclusion, med treatment promotes new bone regeneration and healing at the injury site by activating Wnt/canonical and notch signaling pathways. This study also forms a strong case for evaluation of med in delayed union and non-union fracture cases.

Bone regeneration in osteoporosis by delivery BMP-2 and PRGF from tetronic–alginate composite thermogel

Bone regeneration in osteoporosis and fragility fractures which are highly associated with age remains a great challenge in the orthopedic field, even though the bone is subjected to a continuous process of remodeling which persists throughout lifelong. Regulation of osteoblast and osteoclast differentiation is recognized as effective therapeutic targets to accelerate bone regeneration in osteopenic conditions. Anthocyanins (ACNs), a class of naturally occurring compounds obtained from colored plants, have received increasing attention recently because of their well-documented biological effects, such as antioxidant, anti-inflammation, and anti-apoptosis in chronic diseases, like osteoporosis. Here, we summarized the detailed research progress on ACNs on bone regeneration and their molecular mechanisms on promoting osteoblast differentiation as well as inhibiting osteoclast formation and differentiation to explore their promising therapeutic application in repressing bone loss and helping fragility fracture healing. Better understanding the role and mechanisms of ACNs on bone regeneration is helpful for the prevention or treatment of osteoporosis and also for the exploration of new bone regenerative medicine.

Injectable, anti-collapse, adhesive, plastic and bioactive bone graft substitute promotes bone regeneration by moderating oxidative stress in osteoporotic bone defect

Evidence-based medicine is switching from the analysis of single diseases at a time toward an integrated assessment of a diseased person. Complementary and alternative medicine (CAM) offers multiple holistic approaches, including osteopathy, homeopathy, chiropractic, acupuncture, herbal and energy medicine and meditation, all potentially impacting on major human diseases. It is now becoming evident that acupuncture can modify the expression of different endorphin genes and the expression of genes encoding for crucial transcription factors in cellular homeostasis. Extremely low frequency magnetic fields have been found to prime the commitment to a myocardial lineage in mouse embryonic stem cells, suggesting that magnetic energy may direct stem cell differentiation into specific cellular phenotypes without the aid of gene transfer technologies. This finding may pave the way to novel approaches in tissue engineering and regeneration. Different ginseng extracts have been shown to modulate growth and differentiation in pluripotent cells and to exert wound-healing and antitumor effects through opposing activities on the vascular system, prompting the hypothesis that ancient compounds may be the target for new logics in cell therapy. These observations and the subtle entanglement among different CAM systems suggest that CAM modalities may deeply affect both the signaling and transcriptional level of cellular homeostasis. Such a perception holds promises for a new era in CAM, prompting reproducible documentation of biological responses to CAM-related strategies and compounds. To this end, functional genomics and proteomics and the comprehension of the cell signaling networks may substantially contribute to the development of a molecular evidence–based CAM.

Objectives: Stem cell-based tissue engineering approaches are promising for bone repair and regeneration. Periodontal ligament stem cells (PDLSCs) are a promising cell source for tissue engineering, especially for maxillofacial bone and periodontal regeneration. Many studies have shown potent results via PDLSCs in bone regeneration. In this review, we describe recent cutting-edge researches on PDLSC-based bone regeneration and periodontal tissue regeneration. Data and sources: An extensive search of the literature for papers related to PDLSCs-based bioactive constructs for bone tissue engineering was made on the databases of PubMed, Medline and Google Scholar. The papers were selected by three independent calibrated reviewers. Results: Multiple types of materials and scaffolds have been combined with PDLSCs, involving xeno genic bone graft, calcium phosphate materials and polymers. These PDLSC-based constructs exhibit the potential for bone and periodontal tissue regeneration. In addition, various osteo inductive agents and strategies have been applied with PDLSCs, including drugs, biologics, gene therapy, physical stimulation, scaffold modification, cell sheets and co-culture. Conclusoin: This review article demonstrates the great potential of PDLSCs-based bioactive constructs as a promising approach for bone and periodontal tissue regeneration.

Notch1-4 receptors and their signaling pathways are expressed in almost all organ systems and play a pivotal role in cell fate decision by coordinating cell proliferation, differentiation and apoptosis. Differential expression and activation of Notch signaling pathways has been observed in a variety of organs and tissues under physiological and pathological conditions. Bone tissue represents a dynamic system, which is constantly remodeled throughout life. In bone, Notch receptors have been shown to control remodeling and regeneration. Numerous functions have been assigned to Notch receptors and ligands, including osteoblast differentiation and matrix mineralization, osteoclast recruitment and cell fusion and osteoblast/osteoclast progenitor cell proliferation. The expression and function of Notch1-4 in the skeleton are distinct and closely depend on the temporal expression at different differentiation stages. This review addresses the current knowledge on Notch signaling in adult bone with emphasis on metabolism, bone regeneration and degenerative skeletal disorders, as well as congenital disorders associated with mutant Notch genes. Moreover, the crosstalk between Notch signaling and other important pathways involved in bone turnover, including Wnt/β-catenin, BMP and RANKL/OPG, are outlined.

Bone defects caused by aging populations and accidental injuries have a significant impact on human life, making bone repair and regeneration a research hotspot. The piezoelectric effect in biomaterials has shown great potential in bone defect treatment by converting mechanical stress into electrical signals to promote osteoblast behavior and subsequently accelerate bone regeneration. Electrical stimulation has been proven to improve the interfacial properties of biomaterials, enhancing cell adhesion and growth on the material surface, and promoting bone healing by regulating cellular behavior. With ongoing research on self-powered materials, various electroactive biomaterials have emerged. This review summarizes the mechanisms of bone repair and regeneration under electrical stimulation and the role of self-powered biomaterials in promoting bone regeneration by regulating the microenvironment. We present examples of applications combining biomaterials and electrical stimulation and discuss the challenges and future directions of these strategies for clinical translation. In conclusion, electroactive biomaterials show remarkable promise in bone defect treatment and provide a new therapeutic approach for bone regeneration.

Bone regeneration procedures aim at recapitulating optimal wound healing where tissue components are restored to the form and function required for tissue and organ homeostasis (Zohar T Bueno G Dimitriou et al. 2011). Examples of ideal bone regeneration include the healing of a healthy tooth extraction socket or a simple bone fracture. This is not the case in non-union fractures, or extensive damage as a result of tumour removal or bone subjected to chemotherapy, where the overall wound healing ability may be compromised (Dimitriou et al. 2011). Bone is a specialized connective tissue consisting of osteoblasts, osteocytes and osteoclasts embedded in a mineralized matrix capable of remodelling, renewing and load bearing. Optimal bone regenerative therapy will enhance mineralized tissue wound healing through enrichment of the wound/bone defect with a matrix scaffold to support the wound, cells that will give rise to osteoprogenitors and inducer molecules, such as growth factors to amplify activity of cells or events responsible for bone formation. New regenerative approaches may include a combination of these factors in part or as a whole. The temporal, spatial activity and maturation of these three components (i.e. cells, matrix and inducer molecules) during bone regeneration has to be a coordinated and integrative process. Delayed, reduced or lack of activity of any of these components may result in repair and not regeneration of a remodelling functional bone. Cell therapy is compared to the gold standard of autogenous bone marrow grafting, which is considered to be enriched with mesenchymal stem cells, osteoprogenitors and inducer molecules; marrow grafting usually offers predicative regenerative approach. Matrix grafting has to offer mechanical support for the regenerative process to interact with the differentiating osteoprogenitor cells and provide the conditions for the cells to deposit host bone matrix. Grafted inducer molecules need to interact with both the developed matrix and differentiating osteoprogenitors to assure bone matrix deposition and mineralization (Figure 1).