Osteoblast Activity Research Articles

HT-2 mycotoxin and selenium deficiency: Effects on Femur development and integrity in Young mice

Kashin-Beck Disease (KBD), an osteoarticular disorder, is potentially influenced by several factors, among which selenium deficiency and HT-2 mycotoxin exposure are considered significant. However, the combined effect of these factors on femoral development remains unclear, Conducted over eight weeks on forty-eight male mice categorized into control, selenium-deficient, and HT-2 toxin-exposed groups, including dual-exposure sets, this study comprehensively monitored body weight, bone metabolism markers, and cellular health. Employing biomechanical analysis, micro-computed tomography (micro-CT), and transmission electron microscopy (TEM), we unearthed a reduction in body weight due to HT-2 toxin alone, with selenium deficiency exacerbating these effects synergistically. Our results unveil that both factors independently affect bone metabolism, yet their confluence leads to a pronounced degradation of bone health parameters, including alterations in calcium, phosphorus, and vitamin D levels, alongside marked changes in osteoblast and osteoclast activity and bone cell structures. The notable damage to femoral cortical and trabecular architectures underscores the perilous interplay between dietary selenium absence and HT-2 toxin presence, necessitating a deeper understanding of their separate and joint effects on bone integrity. These discoveries underscore the imperative for a nuanced approach to toxicology research and public health policy, highlighting the pivotal influence of environmental and nutritional factors on skeletal well-being.

Investigation of the Effects of Thymoquinone and Dental Pulp-Derived Mesenchymal Stem Cells on Tibial Bone Defect Models.

The thymoquinone obtained from Nigella sativa increases osteoblastic activity and significantly reduces the number of osteoclasts, thereby accelerating bone healing. In addition, mesenchymal stem cells isolated from various tissues are considered a potential cell source for bone regenerative therapies. The aim of this study is to investigate the effectiveness of thymoquinone, a current and novel agent, in combination with mesenchymal stem cells derived from the dental pulp in promoting bone healing. In the study, 28 male Sprague Dawley rats were used. The rats were divided into 4 groups, each consisting of 7 rats: the control group (group 1) (n=7), thymoquinone group (group 2) (n=7), stem cell group (group 3) (n=7), stem cell+thymoquinone group (group 4) (n=7). A bone defect of 4mm in diameter and 5mm in length was created in the left tibial bones of all rats with a trephine bur. In group 1, no procedure was applied to the defect area. Group 2 was applied thymoquinone (10mg/kg) with oral gavage. In group 3, stem cells were used locally to the defect area. In group 4, stem cells and thymoquinone (10mg/kg) was applied to the defect area. All rats were killed on the 28th day of the experiment. Tibia tissues extracted during sacrifice were histomorphologically examined in a fixative solution. Significant differences were found in terms of new bone formation and osteoblastic activity values in the "thymoquinone" ( P <0.05), "stem cell" ( P <0.05), and "stem cell+thymoquinone" ( P <0.05) groups compared to the "control" group. In addition, while there was no significant difference in the "thymoquinone" group compared to these stem cell+thymoquinone group in terms of osteoblastic activity ( P >0.05), the difference in terms of new bone formation was found to be significantly lower. No significant differences among the other groups were observed in new bone formation and osteoblastic activity ( P >0.05). According to the results of our study, stem cell+thymoquinone treatment for bone defects is not only more effective than thymoquinone or stem cell treatment alone but also induces greater development of bone trabeculae, contributes to the matrix and connective tissue formation, and increases the number of osteoblasts and osteocytes involved in bone formation.

Characterization of a spontaneous osteopetrosis model using RANKL-dysfunctional mice

Tumor necrosis factor superfamily member 11 (TNFSF11), or receptor activator of nuclear factor-κB ligand (RANKL), is a crucial osteoclast-stimulating factor binding to RANK on osteoclast membranes. Mouse models are powerful tools for understanding the genetic mechanisms of related diseases. Here, we examined the utility of Tnfsf11 mutation in mice for understanding the mechanisms of bone remodeling and dysmorphology. The Tnfsf11gum mouse, discovered in 2011 at Jackson Laboratory, was used to study the genetic landscape associated with TNFSF11 inactivation in bone marrow tissues. Tnfsf11gum/+ and Tnfsf11+/+ mice were subjected to Micro-CT observation, ELISA analysis, histological evaluation, and massively-parallel mRNA sequencing (RNA-Seq) analysis. Tnfsf11gum/+ mice exhibited severe osteopetrotic changes in the bone marrow cavity, along with significantly lower serum RANKL levels and a reduced number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts in the bone marrow compared to those in Tnfsf11+/+ mice. However, tooth eruption between Tnfsf11gum/+ and Tnfsf11+/+ mice did not differ. Furthermore, genes involved in osteoblast proliferation and differentiation, including Gli1, Slc35b2, Lrrc17, and Junb were differentially expressed. Heterozygous mutation of TNFSF11 was also associated with a slightly increased expression of genes involved in osteoclast proliferation and differentiation, including Tcirg1, Junb, Anxa2, and Atp6ap1. Overall, we demonstrate that single gene mutations in Tnfsf11 cause bone resorption instability without significantly altering the genes related to osteoblast and osteoclast activity in the bone marrow cavity, thus establishing an optimal resource as an experimental animal model for bone resorption in bone biology research.

Iron and bones: effects of iron overload, deficiency and anemia treatments on bone.

Iron is a vital trace element and exerts opposing effects on bone in both iron overload and iron deficiency situations. Remarkably, iron supplementation through intravenous infusion in patients with iron deficiency can also have detrimental effects on bone in special cases. The diverse mechanisms underlying these effects and their manifestations contribute to the complexity of this relationship. Iron overload impacts both bone resorption and formation, accelerating bone resorption while reducing bone formation. These effects primarily result from the direct action of reactive oxygen species (ROS), which influence the proliferation, differentiation, and activity of both osteoclasts and osteoblasts differently. This imbalance favors osteoclasts and inhibits the osteoblasts. Simultaneously, multiple pathways, including bone morphogenic proteins, RANK ligand, and others, contribute to these actions, leading to a reduction in bone mass and an increased susceptibility to fractures. In contrast, iron deficiency induces low bone turnover due to energy and co-factor deficiency, both of which require iron. Anemia increases the risk of fractures in both men and women. This effect occurs at various levels, reducing muscular performance and, on the bone-specific level, decreasing bone mineral density. Crucially, anemia increases the synthesis of the phosphaturic hormone iFGF23, which is subsequently inactivated by cleavage under physiological conditions. Thus, iFGF23 levels and phosphate excretion are not increased. However, in specific cases where anemia has to be managed with intravenous iron treatment, constituents-particularly maltoses-of the iron infusion suppress the cleavage of iFGF23. As a result, patients can experience severe phosphate wasting and, consequently, hypophosphatemic osteomalacia. This condition is often overlooked in clinical practice and is often caused by ferric carboxymaltose. Ending iron infusions or changing the agent, along with phosphate and vitamin D supplementation, can be effective in addressing this issue.

Bone-to-Implant Contact in Implants with Plasma-Treated Nanostructured Calcium-Incorporated Surface (XPEEDActive) Compared to Non-Plasma-Treated Implants (XPEED): A Human Histologic Study at 4 Weeks

Titanium implants undergo an aging process through surface hydrocarbon deposition, resulting in decreased wettability and bioactivity. Plasma treatment was shown to significantly reduce surface hydrocarbons, thus improving implant hydrophilicity and enhancing the osseointegration process. This study investigates the effect of plasma surface treatment on bone-to-implant contact (BIC) of implants presenting a nanostructured calcium-incorporated surface (XPEED®). Following a Randomized Controlled Trial (RCT) design, patients undergoing implant surgery in the posterior maxilla received additional plasma-treated (n = 7) or -untreated (n = 5) 3.5 × 8 mm implants that were retrieved after a 4-week healing period for histological examination. Histomorphometric analysis showed that plasma-treated implants exhibited a 38.7% BIC rate compared to 22.4% of untreated implants (p = 0.002), indicating enhanced osseointegration potential. Histological images also revealed increased bone formation and active osteoblastic activity around plasma-treated implants when compared to untreated specimens. The findings suggest that plasma treatment improves surface hydrophilicity and biological response, facilitating early bone formation around titanium implants. This study underscores the importance of surface modifications in optimizing implant integration and supports the use of plasma treatment to enhance osseointegration, thereby improving clinical outcomes in implant dentistry and offering benefits for immediate and early loading protocols, particularly in soft bone conditions.

Intersecting Paths: Unraveling the Complex Journey of Cancer to Bone Metastasis.

The phenomenon of bone metastases presents a significant challenge within the context of advanced cancer treatments, particularly pertaining to breast, prostate, and lung cancers. These metastatic occurrences stem from the dissemination of cancerous cells into the bone, thereby interrupting the equilibrium between osteoblasts and osteoclasts. Such disruption results in skeletal complications, adversely affecting patient morbidity and quality of life. This review discusses the intricate interplay between cancer cells and the bone microenvironment, positing the bone not merely as a passive recipient of metastatic cells but as an active contributor to cancer progression through its distinctive biochemical and cellular makeup. A thorough examination of bone structure and the dynamics of bone remodeling is undertaken, elucidating how metastatic cancer cells exploit these processes. This review explores the genetic and molecular pathways that underpin the onset and development of bone metastases. Particular emphasis is placed on the roles of cytokines and growth factors in facilitating osteoclastogenesis and influencing osteoblast activity. Additionally, this paper offers a meticulous critique of current diagnostic methodologies, ranging from conventional radiography to advanced molecular imaging techniques, and discusses the implications of a nuanced understanding of bone metastasis biology for therapeutic intervention. This includes the development of targeted therapies and strategies for managing bone pain and other skeletal-related events. Moreover, this review underscores the imperative of ongoing research efforts aimed at identifying novel therapeutic targets and refining management approaches for bone metastases. It advocates for a multidisciplinary strategy that integrates advancements in medical oncology and radiology with insights derived from molecular biology and genetics, to enhance prognostic outcomes and the quality of life for patients afflicted by this debilitating condition. In summary, bone metastases constitute a complex issue that demands a comprehensive and informed approach to treatment. This article contributes to the ongoing discourse by consolidating existing knowledge and identifying avenues for future investigation, with the overarching objective of ameliorating patient care in the domain of oncology.

A comparative investigation of the effects of Resveratrol and dental pulp delivered mesenchimal stem cells on rat tibia bone defect healing

Resveratrol (3,4,5–trihydroxystilbene), an antioxidant compound, has a natural phytoalexin structure and also has many properties such as anti–inflammatory, antineoplastic and antiplatelet. In addition, mesenchymal stem cells isolated from various tissues are considered as a potential cell source for bone regenerative therapies. The present study aims to examine the effects of Resveratrol and dental pulp–derived mesenchymal stem cells on new bone formation in rats, both isolated and combined, by immunohistochemical methods. Twenty eigth Spraque Dawley male rats were used in the study. The rats were divided into four groups with seven rats in each group; the control group (Group 1) (n=7), the Systemic Resveratrol group (Group 2) (n=7), the Stem cell group (Group 3) (n=7), the Stem cell + Systemic Resveratrol group (Group 4) (n=7). A defect was opened on the tibia bones of the rats in all groups with a trephane bur (diameter of 3 mm and a length of 4 mm). After the 4–week experiment, all rats were sacrificed following the experimental protocols specific to each group. The specimens of tibia were subjected to histomorphological examination in fixative solutions. Values of inflammation, connective tissue formation, osteoclastic activity, osteoblast values, new bone formation, BMP2 and BMP4 expression levels obtained for all groups were evaluated by statistical analysis. Compared to the control group, new bone formation and osteoblastic activity were found to be significantly higher in the Stem cell group and Stem cell + Systemic Resveratrol group. (P=0.001) Additionally, new bone formation in the Systemic Resveratrol group was found to be significantly lower than in the Stem cell + Systemic Resveratrol group. (P=0.006) No significant difference was observed between other groups. (P&gt;0.05) According to the results of the study, it was observed that Stem cell + Resveratrol treatment was more effective than isolated Resveratrol or isolated stem cell treatment applications, it induced the development of more bone trabeculae, decrease inflammation and increased the number of osteoblasts involved in bone formation. In the light of these data, it was concluded that the combined use of Resveratrol and Stem cells is more effective on the healing of bone defects than their isolated use.

The Species Effect: Differential Sphingosine-1-Phosphate Responses in the Bone in Human Versus Mouse.

The deterioration of osteoblast-led bone formation and the upregulation of osteoclast-regulated bone resorption are the primary causes of bone diseases, including osteoporosis. Numerous circulating factors play a role in bone homeostasis by regulating osteoblast and osteoclast activity, including the sphingolipid-sphingosine-1-phosphate (S1P). However, to date no comprehensive studies have investigated the impact of S1P activity on human and murine osteoblasts and osteoclasts. We observed species-specific responses to S1P in both osteoblasts and osteoclasts, where S1P stimulated human osteoblast mineralisation and reduced human pre-osteoclast differentiation and mineral resorption, thereby favouring bone formation. The opposite was true for murine osteoblasts and osteoclasts, resulting in more mineral resorption and less mineral deposition. Species-specific differences in osteoblast responses to S1P were potentially explained by differential expression of S1P receptor 1. By contrast, human and murine osteoclasts expressed comparable levels of S1P receptors but showed differential expression patterns of the two sphingosine kinase enzymes responsible for S1P production. Ultimately, we reveal that murine models may not accurately represent how human bone cells will respond to S1P, and thus are not a suitable model for exploring S1P physiology or potential therapeutic agents.

Hyperthyroidism-driven bone loss depends on BMP receptor Bmpr1a expression in osteoblasts

Hyperthyroidism is a well-known trigger of high bone turnover that can lead to the development of secondary osteoporosis. Previously, we have shown that blocking bone morphogenetic protein (BMP) signaling systemically with BMPR1A-Fc can prevent bone loss in hyperthyroid mice. To distinguish between bone cell type-specific effects, conditional knockout mice lacking Bmpr1a in either osteoclast precursors (LysM-Cre) or osteoprogenitors (Osx-Cre) were rendered hyperthyroid and their bone microarchitecture, strength and turnover were analyzed. While hyperthyroidism in osteoclast precursor-specific Bmpr1a knockout mice accelerated bone resorption leading to bone loss just as in wildtype mice, osteoprogenitor-specific Bmpr1a deletion prevented an increase of bone resorption and thus osteoporosis with hyperthyroidism. In vitro, wildtype but not Bmpr1a-deficient osteoblasts responded to thyroid hormone (TH) treatment with increased differentiation and activity. Furthermore, we found an elevated Rankl/Opg ratio with TH excess in osteoblasts and bone tissue from wildtype mice, but not in Bmpr1a knockouts. In line, expression of osteoclast marker genes increased when osteoclasts were treated with supernatants from TH-stimulated wildtype osteoblasts, in contrast to Bmpr1a-deficient cells. In conclusion, we identified the osteoblastic BMP receptor BMPR1A as a main driver of osteoporosis in hyperthyroid mice promoting TH-induced osteoblast activity and potentially its coupling to high osteoclastic resorption.

ROS-scavenging bioactive scaffold orchestrates bone regeneration for osteoporotic bone defect repair

The repair of osteoporotic bone defects, particularly those with irregular shapes, remains a significant challenge due to insufficient bone regeneration and an abnormal level of reactive oxygen species (ROS), which impairs the balance of bone remodeling. Materials that intrinsically regulate ROS to rebalance the activation of osteoblasts and osteoclasts represent a highly desirable alternative to current grafting strategies for the management of osteoporotic defects. Inspired by the tea polyphenols and natural extracellular matrix of bone tissue, a novel biomimetic composite scaffold, the epichlorohydrin-crosslinked hydroxyethyl cellulose/soy protein isolate/polydopamine-coated hydroxyapatite composite sponge (EHSS/PHA) scaffold was designed to orchestrate bone-forming bone marrow mesenchymal stem cells (BMSCs) and bone-resorbing osteoclasts for the rejuvenation of osteoporotic bone defect repair. Benefiting from the distinctive capabilities of the EHSS/PHA, including scavenging active oxygen and osteoinduction, we found that the EHSS/PHA could inhibit the formation of osteoclasts and promote osteogenesis of BMSCs by up-regulating the ratio of Opg/Rankl and activating the β-catenin signaling pathway in an oxidative stress environment. With its antioxidant ability, osteogenic, and self-deploying capability, EHSS/PHA effectively promoted the repair of tibial defects in osteoporotic rats by removing excess reactive oxygen species at the defect site. Taken together, this work presents the EHSS/PHA with multifunctional properties that provide new insight into osteoporotic bone defects.

Research Progress on Inhibition of Osteoclast Differentiation by Traditional Chinese Medicine

Background: Bone tissue undergoes continuous remodeling to maintain a steady state of bone equilibrium. During this process, osteoblasts actively stimulate bone formation, while osteoclasts continuously engage in bone resorption. The dynamic equilibrium between bone formation and bone resorption is crucial for maintaining bone structure. In a healthy human skeletal structure, the two components are constantly in a state of benign dynamic equilibrium. However, due to factors such as aging, trauma, bone diseases, and other influences, the activity of osteoblasts decreases while the activity of osteoclasts increases. This disrupts the dynamic equilibrium, leading to a decrease in bone metabolism. As a result, bone resorption gradually surpasses bone production, making it challenging to maintain a normal amount of bone mass. The effectiveness of traditional Chinese medicine in treating bone-related disorders is extraordinary, and its molecular biological mechanism has become a widely discussed subject. Objectives: This study aims to unravel the classical signaling pathways and potential targets involved in the effects of traditional Chinese medicine on osteoclast differentiation, and to provide evidence for its clinical efficacy. Methodology: The main keywords chosen for this study were “Traditional Chinese Medicine (TCM)”, “osteoclast differentiation”, “natural plant”, and “medicinal plant”. To gather relevant literature, we utilized multiple online search engines, including PubMed, Web of Science, and CNKI, as well as other publication resources. Results: The results indicated that Traditional Chinese Medicine (TCM) can modulate signaling pathways, including NF-κB, MAPKs, STATs, and Wnt/β-catenin pathways., to influence osteoclast differentiation. This modulation involves maintaining the balance of inflammatory interactions, inhibiting oxidative stress. Conclusion: The impact of traditional Chinese medicine on osteoclast differentiation is reflected on multiple levels and through various pathways. Future research is envisioned to delve deeper from the perspective of precision-targeted therapy, aiming to provide insights for identifying the core targets of traditional Chinese medicine in treating orthopedic diseases.

Effect of TiO2 Nanotubes on Biological Activity of Osteoblasts and Focal Adhesion Kinase/Osteopontin Level

Osteoblasts are important cells for bone formation and play a major part in bone diseases and bone defects. Clinically, we usually adopt bone implants for related diseases. Also, nanotechnology is important in bones and joints. This study assessed the effects of TiO2 nanotubes of different diameters on osteoblast activity, FAK and OPN levels, aiming to provide an experimental foundation for selection of clinical bone implant materials. The morphology of MG-63 human osteosarcoma cells changed with expansion of TiO2 nanotubes’ diameter. From the biological activity, the cell proliferation and adhesion were enhanced as the diameter of the TiO2 nanotube was increased and its proliferation and adhesion were highest in the 100 nm TiO2 nanotube, which is related to increased ALP activity, FAK and OPN protein and mRNA expression. ELISA detected ALP activity and found that MG-63 cells cultured with 70 nm nanotube had strongest activity. Immune blotting and PCR results showed that, FAK and OPN activities were highest in 70 nm TiO2 nanotube cells. In summary, TiO2 nanotubes increased cell proliferation and adhesion by up-regulating the activities of FAK and OPN in a concentration-dependent relationship.

Osteomesopyknosis associated with a novel ALOX5 variant that impacts the RANKL pathway.

Bone tissue homeostasis relies on the coordinated activity of the bone-forming osteoblasts and bone-resorbing osteoclasts. Osteomesopyknosis is considered a distinctive rare sclerosing skeletal disorder of unelucidated pathophysiology and presumably autosomal dominant transmission. However, the causal genes are unknown. We present a case report encompassing clinical assessments, imaging studies, and whole-exome sequencing analysis, complemented by functional invitro experiments. This new case of osteomesopyknosis was associated with a missense ALOX5 variant predicted to induce protein misfolding and proteasomal degradation. Transfection experiments demonstrated that the variant was associated with reduced protein levels restored by proteasomal inhibition with bortezomib. Likewise, gene expression analysis showed that the mutated gene was associated with a decreased RANKL/OPG ratio, which is a critical driver of osteoclast precursor differentiation. Our data indicate impaired bone resorption as the underlying mechanism of this rare osteosclerosis, implicating ALOX5 pathogenic variants as potential etiological factors.

Effect of Photobiomodulation Therapy in Type 2 Diabetic Patients on Peri-implant Osteoblastic Activity, Soft-tissue Healing, and Postoperative Pain Discomfort: A Pilot Study

Effect of Photobiomodulation Therapy in Type 2 Diabetic Patients on Peri-implant Osteoblastic Activity, Soft-tissue Healing, and Postoperative Pain Discomfort: A Pilot Study

On the Ion Implantation Synthesis of Ag-Embedded Over Sr-Substituted Hydroxyapatite on a Nano-Topography Patterned Ti for Application in Acetabular Fracture Sites.

There is an ongoing need for improved healing response and expedited osseointegration on the Ti implants in acetabular fracture sites. To achieve adequate bonding and mechanical stability between the implant surface and the acetabular fracture, a new coating technology must be developed to promote bone integration and prevent bacterial growth. A cylindrical Ti substrate mounted on a rotating specimen holder was used to implant Ca2+, P2+, and Sr2+ ions at energies of 100 KeV, 75 KeV and 180 KeV, respectively, using a low-energy accelerator to synthesize strontium-substituted hydroxyapatite at varying conditions. Ag2+ ions of energy 100 KeV were subsequently implanted on the as-formed surface at the near-surface region to provide anti-bacterial properties to the as-formed specimen. The properties of the as-formed ion-implanted specimen were compared with the SrHA-Ag synthesized specimens by cathodic deposition and low-temperature high-speed collision technique. The adhesion strength of the ion-implanted specimen was 43 ± 2.3 MPa, which is well above the ASTM standard for Ca-P coating on Ti. Live/dead cell analysis showed higher osteoblast activity on the ion-implanted specimen than the other two. Ag in the SrHA implanted Ti by ion implantation process showed superior antibacterial activity. In the ion implantation technique, nano-topography patterned surfaces are not concealed after implantation, and their efficacy in interacting with the osteoblasts is retained. Although all three studies examined the antibacterial effects of Ag2+ ions and the ability to promote bone tissue formation by MC3T3-E1 cells on SrHA-Ag/Ti surfaces, ion implantation techniques demonstrated superior ability. The synthesized specimen can be used as an effective implant in acetabular fracture sites based on their mechanical and biological properties.

Repair of Rat Calvarial Critical-Sized Defects Using Heparin-Conjugated Fibrin Hydrogel Containing BMP-2 and Adipose-Derived Pericytes.

The repair of critical-sized calvarial defects is a challenging problem for orthopedic surgery. One of the promising strategies of bone bioengineering to enhance the efficacy of large bone defect regeneration is the combined delivery of stem cells with osteoinductive factors within polymer carriers. The purpose of the research was to study the regenerative effects of heparin-conjugated fibrin (HCF) hydrogel containing bone morphogenetic protein 2 (BMP-2) and adipose-derived pericytes (ADPs) in a rat critical-sized calvarial defect model. In vitro analysis revealed that the HCF hydrogel was able to control the BMP-2 release and induce alkaline phosphatase (ALP) activity in neonatal rat osteoblasts. In addition, it was found that eluted BMP-2 significantly induced the osteogenic differentiation of ADPs. It was characterized by the increased ALP activity, osteocalcin expression and calcium deposits in ADPs. In vivo studies have shown that both HCF hydrogel with BMP-2 and HCF hydrogel with pericytes are able to significantly increase the regeneration of critical-sized calvarial defects in comparison with the control group. Nevertheless, the greatest regenerative effect was found after the co-delivery of ADPs and BMP-2 into a critical-sized calvarial defect. Thus, our findings suggest that the combined delivery of ADPs and BMP-2 in HCF hydrogel holds promise to be applied as an alternative biopolymer for the critical-sized bone defect restoration.

The role of LncRNAs and CircRNAs in osteoporosis: a focus on osteogenesis and osteoclastogenesis signaling pathways

Abstract Background Osteoporosis is a crucial health concern interconnected with physical disabilities as well as financial burdens. It arises from an imbalance between osteoblasts and osteoclasts, provoking the reduction of bone mass and the disturbances in bone structure with high fracture risk. Considerable efforts were done to prevent and mitigate this public health issue. Nonetheless, further understanding of the etiopathology of osteoporosis and the underlying genetic and epigenetic pathways is required. Main body Emerging evidence indicates that noncoding RNAs, including long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), play crucial roles as epigenetic regulators in various pathological processes, including osteoporosis. LncRNAs are RNA transcripts with higher structural complexity that are developed owing to their secondary and tertiary structures, which allow them to create different binding sites for other biomolecules, such as DNA, RNA, and proteins. Another class of noncoding RNAs is circRNAs, which have a covalently closed loop structure without the 5′ cap and 3′ polyA tail and are formed by back-splicing of pre-mRNAs. Because of their closed structure, circRNAs are largely stable, resistant to RNA-degrading nucleases, and possess substantially longer circulatory half-lives than linear RNAs. Interestingly, both lncRNAs and circRNAs serve as competing endogenous RNAs by sponging multiple miRNA binding sites as well as interact with RNA-binding proteins (RBPs), thereby controlling the expression of their target genes. Several studies indicated that altered expression of these regulators could influence many biological processes in bone cells. Conclusion The current review provides current opinions on the role and the underlying mechanisms by which lncRNAs and circRNAs affect osteoblastic and osteoclastic activities. The deep understanding of these noncoding RNAs in osteoporosis offers distinctive avenues for innovative treatment strategies.

Titanium Surface Modification Techniques to Enhance Osteoblasts and Bone Formation for Dental Implants: A Narrative Review on Current Advances

Surface modifications for titanium, a material of choice for dental implants, can greatly alter the surface micro/nanotopography and composition of implants, leading to notable enhancements in their hydrophilicity, mechanical properties, osseointegration performance, and antibacterial performance, as well as their impacts on osteoblast activity and bone formation processes. This article aims to update titanium surface modification techniques for dental implants from the past to the present, along with their effects on osteoblasts and bone formation, by thoroughly summarizing findings from published studies. Peer-reviewed articles published in English consisting of in vitro, in vivo, and clinical studies on titanium dental implant surface treatments were searched in Google Scholar, PubMed/MEDLINE, ScienceDirect, and the Scopus databases from January 1983 to December 2023 and included in this review. The previous studies show that implant surface roughness, condition, and hydrophilicity are crucial for osteoblast adhesion and growth. While various techniques enhance osseointegration comparably, one of the most common approaches to accomplishing these properties is sandblasting large-grit acid etching surface treatment and coating with hydroxyapatite or chitosan. In conclusion, this review points out the efficacy of different subtraction and addition techniques in enhancing the surface properties of titanium dental implants, promoting favorable outcomes in terms of osteoblast activity and bone formation in various degrees. However, most existing studies predominantly compare treated and non-treated titanium, revealing a need for more comprehensive studies comparing the effects of various modification techniques. Moreover, further investigation of factors playing a role in the dynamic osseointegration process in addition to osteoblasts and their functions, as well as improved surface modification techniques for the treatment of compromised patients, is greatly required.

Gold doped Wollastonite hybrid nanocomposites as a candidate for bone regeneration/healing applications: Biocompatibility and antimicrobial efficacy

This work investigates the bioactivity of pure Wollastonite and gold-doped Wollastonite nanohybrids synthesized via a wet chemical technique. Doping with gold nanoparticles at different ratios for Wollastonite, where a dramatic decrease in the respective average particle sizes at the lowest doping ratio of 1.25 wt./v%, then the particle size raised gradually with an increase in the content of gold nanoparticles. In addition, a significant increase in the calculated surface area and the cumulative pore volume upon incorporating gold nanoparticles with the lowest doping ratio of 1.25 wt./v% is associated with a slight decrease in the average pore size. Then, a gradual decrease in the calculated surface area and cumulative pore volume with the increase of doping ratio with gold nanoparticles is associated with an increase in average pore size. The results revealed that after two days of incubation for treated MG-63 cells, the W/Au 5 wt./v% showed the significantly highest alkaline phosphatase (ALP) activity among all other concentrations and the control cells. The ALP activity exceeded four mU/mL. After four days of incubation, the ALP activity in all doping ratios was significantly higher than the control cells, with no significant difference among other groups, but lower than ALP levels after two days of incubation. Also, pure Wollastonite and gold-doped Wollastonite nanohybrids, especially the lowest doping ratio of 1.25 wt./v%, have remarkable efficacy in combating E. coli (Gram-negative), S. aureus (Gram-positive) and Candida albicans. In vitro studies showed that pure Wollastonite and gold-doped Wollastonite nanohybrids had minimal cytotoxic effects on osteosarcoma MG-63 cells, while they showed remarkable cell proliferation even at low concentrations. Based on the in-vitro ALP, bioactivity and biocompatibility results, the content of ALP can directly reflect the activity or function of osteoblasts and is positively correlated with the mineralization ability of cells, which shows that pure and gold-doped Wollastonite nanohybrids were suitable candidates for bone regeneration/healing applications.

Tgif1-deficiency impairs cytoskeletal architecture in osteoblasts by activating PAK3 signaling.

Osteoblast adherence to bone surfaces is important for remodeling bone tissue. This study demonstrates that deficiency of TG-interacting factor 1 (Tgif1) in osteoblasts results in altered cell morphology, reduced adherence to collagen type I-coated surfaces, and impaired migration capacity. Tgif1 is essential for osteoblasts to adapt a regular cell morphology and to efficiently adhere and migrate on collagen type I-rich matrices in vitro. Furthermore, Tgif1 acts as a transcriptional repressor of p21-activated kinase 3 (Pak3), an important regulator of focal adhesion formation and osteoblast spreading. Absence of Tgif1 leads to increased Pak3 expression, which impairs osteoblast spreading. Additionally, Tgif1 is implicated in osteoblast recruitment and activation of bone surfaces in the context of bone regeneration and in response to parathyroid hormone 1-34 (PTH 1-34) treatment in vivo in mice. These findings provide important novel insights in the regulation of the cytoskeletal architecture of osteoblasts.