Promote Osteoblast Activity Research Articles

D-limonene suppresses RANKL-induced osteoclast differentiation and promotes osteoblast activity in-vitro.

Treatments for osteoporosis are typically given post-fracture. Therefore, identifying safe prophylactic interventions to reduce fracture risk would be beneficial. One approach is to utilise the bioactive properties of natural compounds to modify osteoclast and osteoblast activity. D-limonene a well-tolerated, anti-inflammatory monoterpene found in citrus fruits holds promise due to its suppressive effect on NFκB, a key regulator of bone cell activity. We found that limonene promoted osteoblast differentiation and bone nodule formation and inhibited RANKL-indued osteoclast formation and bone resorption in-vitro. Limonene also reduced the pro-resorptive signal provided by osteoblast, augmenting markers of osteoblast differentiation (alkaline phosphatase, osterix and osteocalcin) and significantly decreased osteoclastogenic cytokine production (PTHrP, IL-1β and TNF-α). Therefore, limonene supplementation represents a potential route in combination with current interventions to optimise bone cell activity to maintain or enhance bone mass.

Exercise-induced interactions between skeletal muscle and bone via myokines and osteokine in mice: Role of FNDC5/irisin, IGF-1, and osteocalcin

Skeletal muscle and bone interact to maintain their structure and function. Physical exercise is the most effective and easily applicable strategy to maintain their functions; however, exercise-induced interactions by soluble factors remained elusive. Our study aimed to identify exercise-induced interactions between muscle and bone by examining (1) the effects of myokine on bone and (2) the effects of osteocalcin (OCN) on skeletal muscle. To understand the effects of exercise-induced myokines on bone, we examined the effects of FNDC5 for aerobic exercise and IGF-1 for resistance exercise using a muscle-specific myokine overexpression model. To examine OCN effects on muscle, mice were intraperitoneally administered OCN-neutralizing antibody during long-term exercise. Our result showed that aerobic exercise tended to increase serum HA-tag protein attached to FNDC5 in muscle-specific overexpression groups. In addition, osteoblastic activation was increased only after aerobic exercise with HA/FNDC5 overexpression. Resistance exercise did not alter circulating HA-tag (muscle-derived IGF-1) and bone metabolism after IGF-1/HA overexpression. In the OCN study, aerobic exercise enhanced endurance capacity by restoring muscle glycogen content; however, OCN neutralization returned these to baseline. After resistance exercise, OCN suppression inhibited muscle hypertrophy and strength gains by preventing protein synthesis. Our results suggest that aerobic exercise following FNDC5 muscle overexpression promotes osteoblast activity, which may be partially caused by muscle-derived FNDC5 secretion. In addition, OCN was necessary for muscle adaptation in both aerobic and resistance exercises.

Resveratrol reversed rosiglitazone administration induced bone loss in rats with type 2 diabetes mellitus

Rosiglitazone (RSG), as an insulin-sensitizing drug to treat type 2 diabetes mellitus (T2DM) is reported to decrease bone quality and increase bone fracture risk. The multiple off-target effects of Resveratrol (RSV), a natural specific agonist of Sirtuin1 (Sirt1) with pro-osteoblastogenesis and anti-adipogenesis effects, on bone loss in T2DM are still under discussion. In this study, successfully ovariectomized rats were fed with high-fat diet and STZ (HFD/STZ) to induced T2DM mice. RSV alone, RSG alone or co-administration of RSV and RSG were given orally to T2DM rats for 8 weeks to determine whether RSV administration had any prevention effect on T2DM osteoporosis. Bone mesenchymal stem cells (BMSCs) and bone marrow‑derived macrophages (BMMs) were cultured under high glucose condition and were induced to osteoblasts or adipocytes and osteoclasts, respectively. μCT and HE staining showed that in T2DM osteoporotic rats, RSV co-administration prevents RSG induced-bone loss. ELISA results confirmed that RSV suppressed osteoclast activity and promoted osteoblast activity in diabetic osteoporosis rats and RSG-administrated diabetic osteoporosis rats. In vitro study showed that RSV significantly reversed RSG induced inhibition on osteogenesis and promotion on adiopogenesis of BMSC under high glucose (HG). Moreover, RSV significantly reverse RSG induced osteoclast formation and mature under HG. Taken together, these findings uncover a previously unappreciated anti-osteoporosis effect of concomitant treatment with RSV in RSG-administrated diabetic rats, suggesting the clinical use of RSV as an adjuvant in the treatment of T2DM for preventing or reversing RSG administration-associated bone loss.

Studying the Effect of Magnetron Copper Deposition on the Surface Topography of Biodegradable Antibacterial Coating.

The surface properties of the materials used significantly influence the success and longevity of medical implants. Increasing surface roughness promotes osteoblast activity and osseointegration, while biodegradable materials such as copper have shown potential for antimicrobial applications. However, the effect of coating parameters on surface topography is not well investigated. Sputtering of copper was performed using EPOS-PVD-440 system (Zeleno-grad, Russia). The samples were examined by Scanning Electron Microscopy (SEM) with subsequent image processing in Mountains software (Digital Surf). Antibacterial efficacy was evaluated against Staphylococcus aureus by measuring the zone of inhibition. Additionally, copper ion release was monitored over time to assess its correlation with changes in surface topography. Higher sputtering currents increased surface roughness and particle size, with a significant release of copper ions within the first 24 hr of immersion. Samples sputtered at higher currents exhibited coarser grain structures. The release of copper ions in the simulated biological environment led to further changes in surface topography, highlighting the critical influence of sputtering parameters on coating properties. Optimizing magnetron copper deposition parameters enhances the surface topography and antibacterial effectiveness of biodegradable coatings on implants.

Effects of acute- and long-term aerobic exercises at different intensities on bone in mice.

Exercise intensity determines the benefits of aerobic exercise. Our objectives were, in aerobic exercise at different intensities, to determine (1) changes in bone metabolism-related genes after acute exercise and (2) changes in bone mass, strength, remodeling, and bone formation-related proteins after long-term exercise. Total 36 male C57BL/6J mice were divided into a control group and exercise groups at 3 different intensities: low, moderate, or high group. Each exercise group was assigned to acute- or long-term exercise groups. Tibias after acute exercise were evaluated by real-time PCR analysis. Furthermore, hindlimbs of long-term exercise were assessed by micro-CT, biomechanical, histological, and immunohistochemical analyses. Acute moderate-intensity exercise decreased RANKL level as bone resorption marker, whereas low- and high-intensity exercise did not alter it. Additionally, only long-term exercise at moderate intensity increased bone mass and strength. Moderate-intensity exercise promoted osteoblast activity and suppressed osteoclast activity. After low- and high-intensity exercise, osteoblast and osteoclast activity were unchanged. An increase in the number of β-catenin-positive cells and a decrease in sclerostin-positive cells were observed in the only moderate group. These results showed that moderate-intensity exercise can inhibit bone resorption earlier, and long-term exercise can increase bone mass and strength through promoted bone formation via the Wnt/β-catenin activation. High-intensity exercise, traditionally considered better for bone, may fail to stimulate bone remodeling, leading to no change in bone mass and strength. Our findings suggest that moderate-intensity exercise, neither too low nor high, can maintain bone health.

Surface-modified deproteinized human demineralized tooth matrix for bone regeneration: physicochemical characterization and osteoblast cell biocompatibility.

Tooth presents an intriguing option as a bone graft due to its compositional similarity to bone. However, the deproteinized human demineralized tooth matrix (dpDTM), developed to overcome the limited availability of autologous tooth grafts, has suboptimal pore size and surface roughness. This study aimed to fabricate a surface-modified dpDTM using acid etching and collagen coating, followed by in vitro evaluation of physicochemical and biological properties. The dpDTM was modified into two protocols: Acid-modified dpDTM (A-dpDTM) and collagen-modified dpDTM (C-dpDTM). Results demonstrated that A-dpDTM and C-dpDTM had increased pore sizes and rougher surfaces compared to dpDTM. Collagen immobilization was evidenced by nitrogen presence exclusively in C-dpDTM. All groups had a Ca/P molar ratio of 1.67 and hydroxyapatite as the sole constituent, with 65-67% crystallinity. Degradation rates significantly increased to 30% and 20% for C-dpDTM and A-dpDTM, respectively, compared to 10% for dpDTM after 120 days. Cumulative collagen release of C-dpDTM on Day 30 was 45.16 µg/ml. Osteoblasts attachment and proliferation were enhanced on all scaffolds, especially C-dpDTM, which displayed the highest proliferation and differentiation rates. In conclusion, surface modified of dpDTM, including A-dpDTM and C-dpDTM, significantly enhances bioactivity by altering surface properties and promoting osteoblast activity, thereby demonstrating promise for bone regeneration applications.

Exploring the Anti-Osteoporotic Potential of Daucosterol: Impact on Osteoclast and Osteoblast Activities.

Osteoporosis is a debilitating condition characterized by reduced bone mass and density, leading to compromised structural integrity of the bones. While conventional treatments, such as bisphosphonates and selective estrogen receptor modulators (SERMs), have been employed to mitigate bone loss, their effectiveness is often compromised by a spectrum of adverse side effects, ranging from gastrointestinal discomfort and musculoskeletal pain to more severe concerns like atypical fractures and hormonal imbalances. Daucosterol (DC), a natural compound derived from various plant sources, has recently garnered considerable attention in the field of pharmacology. In this study, we investigated the anti-osteoporosis potential of DC by characterizing its role in osteoclasts, osteoblasts, and lipopolysaccharide (LPS)-induced osteoporosis. The inhibitory effect of DC on osteoclast differentiation was determined by tartrate-resistant acid phosphatase (TRAP) staining, F-actin ring formation by fluorescent staining, and bone resorption by pit formation assay. In addition, the calcification nodule deposition effect of osteoblasts was determined by Alizarin red S staining. The effective mechanisms of both cells were verified by Western blot and reverse transcription polymerase chain reaction (RT-PCR). To confirm the effect of DC in vivo, DC was administered to a model of osteoporosis by intraperitoneal administration of LPS. The anti-osteoporosis effect was then characterized by micro-CT and serum analysis. The results showed that DC effectively inhibited osteoclast differentiation at an early stage, promoted osteoblast activity, and inhibited LPS-induced bone density loss. The results of this study suggest that DC can treat osteoporosis through osteoclast and osteoblast regulation, and therefore may be considered as a new therapeutic alternative for osteoporosis patients in the future.

Sustained delivery of osteogenic growth peptide through injectable photoinitiated composite hydrogel for osteogenesis.

One of the most challenging clinical issues continues to be the effective bone regeneration and rebuilding following bone abnormalities. Although osteogenic growth peptide (OGP) has been proven to be effective in promoting osteoblast activity, its clinical application is constrained by abrupt release and easily degradation. We developed a GelMA/HAMA dual network hydrogel loaded with OGP based on a combination of physical chain entanglement and chemical cross-linking effects to produce an efficient long-term sustained release of OGP. The hydrogel polymers were quickly molded under ultraviolet (UV) light and had the suitable physical characteristics, porosity structure and biocompatibility. Significantly, the GelMA/HAMA-OGP hydrogel could promote cell proliferation, adhesion, increase osteogenic-related gene and protein expression in vitro. In conclusion, the OGP sustained-release system based on GelMA/HAMA dual network hydrogel offers a fresh perspective on bone regeneration therapy.

The Synergistic Effect of Zuogui Pill and Eldecalcitol on Improving Bone Mass and Osteogenesis in Type 2 Diabetic Osteoporosis.

Background and Objectives: The incidence of diabetic osteoporosis, an important complication of diabetes mellitus, is increasing gradually. This study investigated the combined effect of the Zuogui pill (ZGP) and eldecalcitol (ED-71), a novel vitamin D analog, on type 2 diabetic osteoporosis (T2DOP) and explored their action mechanism. Materials and Methods: Blood glucose levels were routinely monitored in db/db mice while inducing T2DOP. We used hematoxylin and eosin staining, Masson staining, micro-computed tomography, and serum biochemical analysis to evaluate changes in the bone mass and blood calcium and phosphate levels of mice. Immunohistochemical staining was performed to assess the osteoblast and osteoclast statuses. The MC3T3-E1 cell line was cultured in vitro under a high glucose concentration and induced to undergo osteogenic differentiation. Quantitative real-time polymerase chain reaction, Western blot, immunofluorescence, ALP, and alizarin red staining were carried out to detect osteogenic differentiation and PI3K-AKT signaling pathway activity. Results: ZGP and ED-71 led to a dramatic decrease in blood glucose levels and an increase in bone mass in the db/db mice. The effect was strongest when both were used together. ZGP combined with ED-71 promoted osteoblast activity and inhibited osteoclast activity in the trabecular bone region. The in vitro results revealed that ZGP and ED-71 synergistically promoted osteogenic differentiation and activated the PI3K-AKT signaling pathway. The PI3K inhibitor LY294002 or AKT inhibitor ARQ092 altered the synergistic action of both on osteogenic differentiation. Conclusions: The combined use of ZGP and ED-71 reduced blood glucose levels in diabetic mice and promoted osteogenic differentiation through the PI3K-AKT signaling pathway, resulting in improved bone mass. Our study suggests that the abovementioned combination constitutes an effective treatment for T2DOP.

Orcinol glucoside targeted p38 as an agonist to promote osteogenesis and protect glucocorticoid-induced osteoporosis

BackgroundGlucocorticoids (GC)-induced osteoporosis (GIOP) is the most common cause of secondary osteoporosis, which leads to an increased risk of fracture in patients. The inhibition of the osteoblast effect is one of the main pathological characteristics of GIOP, but without effective drugs on treatment. PurposeThe aim of this study was to investigate the potential effects of orcinol glucoside (OG) on osteoblast cells and GIOP mice, as well as the mechanism of the underlying molecular target protein of OG both in vitro osteoblast cell and in vivo GIOP mice model. MethodsGIOP mice were used to determine the effect of OG on bone density and bone formation. Then, a cellular thermal shift assay coupled with mass spectrometry (CETSA-MS) method was used to identify the target of OG. Surface plasmon resonance (SPR), enzyme activity assay, molecular docking, and molecular dynamics were used to detect the affinity, activity, and binding site between OG and its target, respectively. Finally, the anti-osteoporosis effect of OG through the target signal pathway was investigated in vitro osteoblast cell and in vivo GIOP mice model. ResultsOG treatment increased bone mineral density (BMD) in GIOP mice and effectively promoted osteoblast proliferation, osteogenic differentiation, and mineralization in vitro. The CETSA-MS result showed that the target of OG acting on the osteoblast is the p38 protein. SPR, molecular docking assay and enzyme activity assay showed that OG could direct bind to the p38 protein and is a p38 agonist. The cellular study found that OG could promote p38 phosphorylation and upregulate the proteins expression of its downstream osteogenic (Runx2, Osx, Collagen Ⅰ, Dlx5). Meanwhile, it could also inhibit the nuclear transport of GR by increasing the phosphorylation site at GR226 in osteoblast cell. In vivo GIOP mice experiment further confirmed that OG could prevent bone loss in the GIOP mice model through promoting p38 activity as well as its downstream proteins expression and activity. ConclusionsThis study has established that OG could promote osteoblast activity and revise the bone loss in GIOP mice by direct binding to the p38 protein and is a p38 agonist to improve its downstream signaling, which has great potential in GIOP treatment for targeting p38. This is the first report to identify OG anti-osteoporosis targets using a label-free strategy (CETSA-MS).

Adenovirus-associated anti-miRNA-214 regulates bone metabolism and prevents local osteoporosis in rats.

Objective: We investigated the expression of miRNA-214 in human osteoporotic bone tissue and tested the utility of adeno-associated virus (AAV) expressing a miRNA-214 inhibitor in terms of preventing local osteoporosis of the femoral condyle in a rat model of osteoporosis. Methods: (1) Femoral heads of patients who underwent hip replacements at our hospital because of femoral neck fractures were collected and divided into osteoporosis and non-osteoporosis groups based on preoperative bone mineral density data. MiRNA-214 expression was detected in bone tissues exhibiting obvious bone microstructural changes in the two groups. (2) A total of 144 SD female rats were divided into four groups: the Control, Model, Negative control (Model + AAV), and Experimental (Model + anti-miRNA-214) groups. AAV-anti-miRNA-214 was injected locally into the rat femoral condyles; we explored whether this prevented or treated local osteoporosis. Results: (1) MiRNA-214 expression in the human femoral head was significantly increased in the osteoporosis group. (2) Compared to the Model and Model + AAV groups, the bone mineral density (BMD) and femoral condyle bone volume/tissue volume (BV/TV) ratio in the Model + anti-miRNA-214 group were significantly higher; in addition, the number (TB.N) and thickness (TB.Th) of the trabecular bones were increased (all p < 0.05). MiRNA-214 expression in the femoral condyles of the Model + anti-miRNA-214 group was significantly higher than that in the other groups. The expression levels of the osteogenesis-related genes Alp, Bglap, and Col1α1 increased, while those of the osteoclast-related genes NFATc1, Acp5, Ctsk, Mmp9, and Clcn7 decreased. Conclusion: AAV-anti-miRNA-214 promoted osteoblast activity and inhibited osteoclast activity in the femoral condyles of osteoporotic rats, improving bone metabolism and slowing osteoporosis progression.

The Protective Effect of Zinc on Salt Induced Histological Changes in Femur of Sprague Dawley Rats-Data Driven Approach

Background: Osteoporosis, a degenerative skeletal illness, is a widespread medical issue that can affect a person's way of life. Aim: To evaluate how salt played a protective role in the Sprague Dawley rats' femur's microscopic alterations. Study Design: Random control trial Methodology: The study used 30 female, Sprague Dawley rats aged between 0 and 12 weeks. Three groups of the animals were randomly chosen. For eight weeks, group B rodents received a high salt diet supplemented with zinc (50 mg/kg/day), while group A rats were administered a high salt diet (8% NaCl). The control group's diet was left unaltered. The left femora of the rats were excised during dissection. There was a decalcification process. To quantify the cortical bone, tissue from the mid-shaft of the femur was taken. To acquire five micrometer (m) sections, processing was done. Hematoxylin and Eosin (H&amp;E) was used to stain tissues as a histological parameter. Each group was compared to the others. Statistical analysis: MATLAB was used to conduct the data analysis. Mean+ S.D. was used to express quantitative data. For group comparisons, a 2-sample t-test was used. Statistical significance was defined as p 0.05. Results: Group A of the experimental study had a considerably smaller area of cortical bone from the mid shaft of the femur. When compared to group A, the experimental zinc-administered group B showed statistically significant improvements. Practical Implication: Osteoporosis is a multifactorial disease and numerous micro/macro nutrients and dietary components can influence bone health including high salt intake. Zinc plays a pivotal role in maintenance and growth of skeletal system and its deficiency results in growth failure, epidermal, gastrointestinal, central nervous, immune, skeletal, and reproductive systems disorders so present study was planned. Conclusion: A diet high in salt caused bone loss due to a reduction in the cortex's surface area. By promoting osteoblast activity and preventing bone-resorbing cells, zinc is useful in reducing the negative effects of salt on bones. Keywords: Cortex, Femur, Osteaoprosis, Salt and Zinc

Three-dimensional visualization of neural networks inside bone by Osteo-DISCO protocol and alteration of bone remodeling by surgical nerve ablation

Bone is one of the largest organ systems in humans and is considered to regulate whole-body homeostasis in cooperation with other organs. We have previously reported that a sympathetic or sensory nervous system inside bone regulates bone homeostasis. However, the detailed regulatory mechanism, including the distribution of nerves inside bone, remains unknown. Although a two-dimensional histological analysis has been widely used to evaluate the structure of nerves or blood vessels, the actual structure is more complex, suggesting that it should be evaluated three-dimensionally. Here, we established a novel bone tissue clearing technique (Osteo-DISCO) for murine bones which enabled us to visualize the detailed distribution of nerves or blood vessels inside bone. Interestingly, we found that there is a specific nerve entry site in each long bone and that surgical ablation of the specific nerve fibers entering bone tissue led to decreased bone formation and impaired bone regeneration. Furthermore, we revealed that the administration of calcitonin gene-related peptide (CGRP), which is primarily released from sensory nerves, suppressed the bone loss caused by surgical nerve ablation. An in vitro study also indicated that CGRP directly promotes osteoblast activity, suggesting that sensory nerves inside bone can regulate osteogenesis via the secretion of CGRP.

Eldecalcitol effectively prevents alveolar bone loss by partially improving Th17/Treg cell balance in diabetes-associated periodontitis.

Background: Diabetes-associated periodontitis (DPD) is an inflammatory and destructive disease of periodontal tissues in the diabetic population. The disease is manifested as more severe periodontal destruction and is more difficult to treat when compared with periodontitis (PD). Eldecalcitol (ELD) is a novel active vitamin D3 analog; however, little clinical evidence is available on its role on improving PD and DPD, and its specific mechanisms remain unclear. In this study, we evaluated the preventative effects of ELD toward PD and DPD and explored its underlying molecular mechanisms. Methods: Experimental PD and DPD mouse models were established by ligation combined with lipopolysaccharide (LPS) from Porphyromonas gingivalis injection in C57BL/6J and C57BLKS/J Iar- + Leprdb/+Leprdb (db/db) mice, respectively. Simultaneously, ELD (0.25μg/kg) was orally administered to mice via an intragastric method. Micro-computed tomography (CT), hematoxylin-eosin (HE) staining, immunohistochemistry (IHC), and tartrate-resistant acid phosphatase (TRAP) staining were used to evaluate alveolar bone alterations in vivo. Flow cytometry, immunofluorescence, and real-time polymerase chain reaction (qRT-PCR) were also used to examine gene expression and probe systemic and local changes in Treg and Th17 cell numbers. Additionally, western blotting and immunofluorescence staining were used to examine changes in STAT3/STAT5 signaling. Results: Micro-CT and HE staining showed that the DPD group had higher alveolar bone loss when compared with the PD group. After applying ELD, alveolar bone loss decreased significantly in both PD and DPD groups, and particularly evident in the DPD group. IHC and TRAP staining also showed that ELD promoted osteoblast activity while inhibiting the number of osteoclasts, and after ELD treatment, the receptor activator of nuclear factor-κB ligand (RANKL) to osteoprotegerin (OPG) ratio decreased. More importantly, this decreasing trend was more obvious in the DPD group. Flow cytometry and qRT-PCR also showed that the systemic Th17/Treg imbalance in PD and DPD groups was partially resolved when animals were supplemented with ELD, while immunofluorescence staining and qRT-PCR data showed the Th17/Treg imbalance was partially resolved in the alveolar bone of both ELD supplemented groups. Western blotting and immunofluorescence staining showed increased p-STAT5 and decreased p-STAT3 levels after ELD application. Conclusion: ELD exerted preventative effects toward PD and DPD by partially rectifying Th17/Treg cell imbalance via STAT3/STAT5 signaling. More importantly, given the severity of DPD, we found ELD was more advantageous in preventing DPD.

Key genes and regulatory networks of hypoxic preconditioning on osteoblasts

The purpose of this study was to identify the key genes and pathways involved in hypoxic preconditioning of osteoblasts. Cells of the hypoxic-preconditioning group underwent 10 min of hypoxic cultivation/10 min normoxic cultivation three times before 4 h of hypoxic cultivation. The long-time hypoxia group underwent 4 h of hypoxic cultivation, and the control group cells underwent 4 h of normoxic cultivation. Differences in miRNAs expressed were analyzed by high-throughput sequencing. MiRwalk 3.0 was used to predict the target genes and conduct a Gene Set Enrichment Analysis. The STRING database and Cytoscape were used to explore the hub genes. A total of 8635 genes and 121 pathways are enriched in the hypoxic-preconditioning compared with the long-time hypoxia group, including the hub genes Utp6, Eif3a, Etf1, Rrp12 and Mkks. 8,476 target genes and 121 pathways are enriched in the hypoxic-preconditioning group compared with the control group, including the hub genes Chd7, Cebpa and Fosb, and 9,315 target genes and 131 pathways are enriched in the long-term hypoxia group compared with the control group, including the hub genes Dcun1d2, Ube2d1 and Frk. Hypoxia preconditioning improved cell viability (p < 0.01), enhanced ALP, IL10 and VEGF expression, and inhibited IL6 expression (p < 0.05). Hypoxic preconditioning is an effective method for promoting osteoblast activity.

Facile synthesis of curcumin-containing poly(amidoamine) dendrimers as pH-responsive delivery system for osteoporosis treatment

Osteoporosis is an age-related metabolic disease of bone, resulting in bone pain and even bone fragility and brittle fracture. Inhibiting overactive osteoclasts while promoting osteoblast activity is an ideal way to treat osteoporosis. Previous studies have demonstrated that natural compounds, such as curcumin (Cur) have dual roles both in promoting bone formation and inhibiting bone resorption, making them promising candidates for osteoporosis treatment. However, their poor water solubility, high dosage of curative effect and significant toxicity to other organs have largely limited their clinical translations. In this study, a novel method was reported to conjugate Cur and poly(amidoamine) dendrimers (PAD) using hexachlorocyclotriphosphazene (HCCP) as the linkage through a one-pot reaction, forming stable and uniform Cur loaded nanospheres (HCCP-Cur-PAD, HCP NPs). Owing to the hydrophilicity of PAD and hydrophobicity of Cur, HCP NPs can self-assemble into nanoparticles with particle size of 138.8 ± 78.7 nm and display excellent water dispersity. The loading capacity of Cur can reach 27.2% and it can be released from HCP NPs with pH-responsiveness. In vitro experimental results demonstrated that the HCP NPs entered lysosomes by endocytosis and proved dual anti-osteoporosis effects of inhibiting osteoclasts and promoting osteoblasts.

Age-related decrease in periostin expression may be associated with attenuated fracture healing in old mice.

Older adults suffer more bone fractures with higher rates of healing complications and increased risk of morbidity and mortality. An improved understanding of the cellular and molecular mechanism of fracture healing and how such processes are perturbed with increasing age may allow for better treatment options to manage fractures in older adults. Macrophages are attractive therapeutics due to their role in several phases of fracture healing. After injury, bone marrow-derived macrophages are recruited to the injury and propagate the inflammatory response, contribute to resolution of inflammation, and promote bone regeneration. A tissue resident population of macrophages named osteal macrophages are present in the periosteum and are directly associated with osteoblasts and these cells contribute to bone formation. Here, we utilized bulk RNA sequencing to analyze the transcriptional activity of osteal macrophages from old and young mice present in primary calvarial cultures. Macrophages demonstrated a diverse transcriptional profile, expressing genes involved in immune function as well as wound healing and regeneration. Periostin was significantly downregulated in macrophages from old mice compared to young. Periostin is an extracellular matrix protein with important functions that promote osteoblast activity during bone regeneration. An age-related decrease of periostin expression was verified in the fracture callus of old mice compared to young. Young periostin knockout mice demonstrated attenuated fracture healing outcomes that reflected what is observed in old mice. This study supports an important role of periostin in fracture healing, and therapeutically targeting the age-related decrease in periostin may improve healing outcomes in older populations.

Use of hyaluronic acid for regeneration of maxillofacial bones

Hyaluronic acid (HA) has been widely used in medicine and is currently of particular interest to maxillofacial surgeons. Several applications have been introduced, including those in which HA is used as a scaffold for bone regeneration, either alone or in combination with other grafting materials, to enhance bone growth. This review aims to analyze the available literature on the use of HA for maxillofacial bone regenerative procedures including socket preservation, sinus augmentation, and ridge augmentation. Medline and PubMed databases were searched for relevant reports published between January 2000 and April 2021. Nine publications describing the use of HA to augment bone volume were identified. Although further studies are needed, these findings are encouraging as they suggest that HA could be used effectively used, in combination with graft materials, in maxillofacial bone regenerative procedures. HA facilitates manipulation of bone grafts, improves handling characteristics and promotes osteoblast activity that stimulates bone regeneration and repair.

Cistanche Deserticola for Regulation of Bone Metabolism: Therapeutic Potential and Molecular Mechanisms on Postmenopausal Osteoporosis.

Osteoporosis is a generalized disease of bone that leads to a loss of bone density and bone mass, destruction of bone microstructure, increased brittleness and therefore fracture. At present, the main treatment of Western medicine is drug therapy such as bisphosphonates, calcitriol, vitamin D, etc. However, long-term use of these drugs may bring some adverse reactions. Chinese herbal medicine Cistanche deserticola could regulate bone metabolism by promoting osteoblast activity and inhibiting osteoclast activity with low toxicity and adverse reactions. Therefore, Cistanche deserticola has attracted increasing attention for its efficacy in the prevention and treatment of osteoporosis in recent years. Here we present a literature review of the molecular pathways involved in osteoporosis and the effects of Cistanche deserticola on bone metabolism. Our objective is to clarify the mechanism of Cistanche deserticola in the treatment of osteoporosis.

Use of hyaluronic acid for regeneration of maxillofacial bones: A review

Purpose: Hyaluronic acid (HA) has been used widely in medicine and is currently of particular interest to maxillofacial surgeons. Several applications have been introduced, including those in which HA is used as a scaffold for bone regeneration both alone and in combination with other grafting materials to enhance bone growth. This review aims to analyze the available literature on the use of HA for maxillofacial bone augmentation for prosthetic-driven implant placement procedures. This article also aims to review the specific advantages, applications, and graft materials associated with HA use. Materials and Methods: Medline and PubMed databases were searched for relevant reports published between January 2000 and December 2021. Results and Discussion: Nine publications describing the use of HA to augment bone volume were identified. Administration of HA facilitates surgical manipulation of the graft and promotes osteoblast activity that stimulates bone regeneration and repair. Conclusion: Although further studies are needed, these findings are encouraging, as they suggest that HA might be used effectively together with additional graft materials in maxillofacial bone augmentation procedures.​