Dual-controlled release of PTH(1–34) via microsphere-hydrogel scaffold promotes early 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.

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

This review considers the potential use of bone morphogenetic protein-2 (BMP-2) for bone regeneration in osteoporosis. Studies on the effect of BMP-2 on bone regeneration in vitro and in vivo are analysed. The results of clinical application of osteoinducers and possible complications are described.

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.

Osteoporosis is a bone disorder characterised by low bone mineral density, reduced bone strength, increased bone fragility, and impaired mineralisation of bones causing an increased risk of bone fracture. Several therapies are available for treating osteoporosis which include bisphosphonates, anti-resorptive agents, oestrogen modulators, etc. These therapies primarily focus on decreasing bone resorption and do not assist in bone regeneration or offering permanent curative solutions. Additionally, these therapies are associated with severe adverse events like thromboembolism, increased risk of stroke, and hypocalcaemia. To overcome these limitations, bone regenerative pathways and approaches are now considered to manage osteoporosis. The bone regenerative pathways involved in bone regeneration include wingless-related integration site/β-catenin signalling pathway, notch signalling pathway, calcium signalling, etc. The various regenerative approaches which possess potential to heal and replace the bone defect site include scaffolds, cements, cell therapy, and other alternative medicines. The review focuses on describing the challenges and opportunities in bone regeneration for osteoporosis.

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.

Background. Among the drugs that have a pleiotropic effect on bone, attention is drawn to alfacalcidol – the precursor of the active form of D-hormone. There are studies that have revealed distinctive features of the effect of alfacalcidol on bone regeneration in osteoporosis and in young animals. The purpose was to study bone regeneration after treatment with alfacalcidol in senile animals. Materials and methods. A transcortical defect from the lateral to the medial femur was modeled in rats aged 24 months in the area of the metadiaphysis. A treatment with alfacalcidol was carried out from the 2-nd day and for 10 and 30 days before the animals was withdrawn from the experiment. Histological study of bone regeneration with morphometric analysis of tissues in the areas of callus had been performed. Results. On the 10-th day of the treatment with alfacalcidol in senile animals, connective tissue, osteoid and coarse-fibrous trabecular bone with a high density of osteoblasts were located in the defect area. On the 30-th day in treated animals, the bone tissue of the callus was mature; its area was larger than in untreated animals. In the area of cancellous bone there is a network of newly formed bone trabeculae. Destructive manifestations around the defect were reduced in animals treated with alfacalcidol. In untreated animals there was no dense bone fusion with cortex fragments; trabeculae of cancellous bone were intermittent. In the lateral part of the callus, the area of bone tissue was reduced compared to the medial part. Conclusions. Treatment of animals with alfacalcidol accelerates the formation of bone tissue in the defect and reduces destructive manifestations around the defect compared to untreated animals.

Oral implantology is considered as the treatment of choice for replacing missing teeth in elderly people. However, implant complications may occur in patients with osteoporosis. The pathogenesis underlying osteoporosis is due to an alteration in bone cell response to hormonal, nutritional, and aging factors. For such challenging situations, improved bone regeneration has been shown around dental implants for certain surface modifications. These modifications include coatings of titanium implants with calcium phosphate (CaP) ceramics. Surface coating developments also allow for the addition of organic biomolecules, like growth factors, into the inorganic coatings that increase the bone formation process at the bone-implant interface. The application of therapeutic-based coatings is becoming a rapidly growing research field of interest. CaP-coated implants have the ability to incorporate anti-osteoporotic drugs, which then can be locally released over time from an implant surface in a controlled manner. Thus, it can be anticipated that nontherapeutic and/or therapeutic coated implants can significantly increase low bone density as well as improve impaired bone regeneration in osteoporosis. This review aims to provide a thorough understanding of the underlying mechanisms for impaired bone regeneration around dental implants in osteoporosis. Secondly, the review will focus on biological interactions and beneficial role of the surface-coated (i.e., nontherapeutics and therapeutics) bone implants in osteoporotic bone tissue.

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

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.

BMP delivery systems for bone regeneration: Healthy vs osteoporotic population. Review

Rosuvastatin/calcium carbonate co-precipitated nanoparticles: A novel synergistic approach enhancing local bone regeneration in osteoporotic rat model

Bioinspired mineral hydrogels as nanocomposite scaffolds for the promotion of osteogenic marker expression and the induction of bone regeneration in osteoporosis

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

BackgroundOsteoporosis results from decreased bone mass and disturbed bone structure. Human bone marrow mesenchymal stem cells (hBMSCs) demonstrate robust osteogenic differentiation, a critical process for bone formation. This research was designed to examine the functions of LINC01133 in osteogenic differentiation.MethodsDifferentially expressed lncRNAs affecting osteogenic differentiation in hBMSCs were identified from the GEO database. A total of 74 osteoporosis patients and 70 controls were enrolled. hBMSCs were stimulated to undergo osteogenic differentiation using an osteogenic differentiation medium (OM). RT-qPCR was performed to evaluate LINC01133 levels and osteogenesis-related genes such as osteocalcin, osteopontin, and RUNX2. An alkaline phosphates (ALP) activity assay was conducted to assess osteogenic differentiation. Cell apoptosis was detected using flow cytometry. Dual luciferase reporter assay and RIP assay were employed to investigate the association between miR-214-3p and LINC01133 or CTNNB1. Loss or gain of function assays were conducted to elucidate the impact of LINC01133 and miR-214-3p on osteogenic differentiation of hBMSCs.ResultsLINC01133 and CTNNB1 expression decreased in osteoporotic patients but increased in OM-cultured hBMSCs, whereas miR-214-3p showed an opposite trend. Depletion of LINC01133 suppressed the expression of genes associated with bone formation and ALP activity triggered by OM in hBMSCs, leading to increased cell apoptosis. Nevertheless, this suppression was partially counteracted by the reduced miR-214-3p levels. Mechanistically, LINC01133 and CTNNB1 were identified as direct targets of miR-214-3p.ConclusionsOur study highlights the role of LINC01133 in positively regulating CTNNB1 expression by inhibiting miR-214-3p, thereby promoting osteogenic differentiation of BMSCs. These findings may provide valuable insights into bone regeneration in osteoporosis.