Bone Cell Activity Research Articles

Cardenolides; calotropin and gomphogenin from Calotropis procera (Aiton) mitigate bone turnover in ovariectomized osteoporotic rats: Targeting RANKL/OPG axis and estrogen receptor-alpha

The present study aimed to examine the effect of Calotropis procera (Aiton) and its major cardenolides; calotropin and gomphogenin on ovariectomy-induced osteoporosis in rats. Osteoporotic rats were orally treated with C. procera alcoholic extract (100 mg/kg), calotropin (CLT; 100 μg/kg) and gomphogenin (GPG; 100 μg/kg) for 14 consecutive days. Bone resorption/formation biomarkers; bone specific alkaline phosphatase (BALP), osteoprotegerin (OPG) and nuclear factor-κβ ligand (RANKL) as well as serum calcium and phosphorus were assessed 24 h after last doses of treatments. Serum levels of estradiol (E2) and catalase were also measured.Oral treatment with C. procera extract, CLT and GPG caused E2 restoration to normal level with a marked regulation in the RANKL/OPG axis. Serum phosphorus and calcium were up-leveled whereas BALP was downregulated. Histopathological examination, bone histomorphometric analysis and immunohistochemical staining for osteopontin (OPN) inspection further emphasized the aforementioned outcomes. The results revealed the superiority of CLT and to a lesser extent GPG osteoporotic effect over C. procera extract. Molecular docking of the two compounds on ER-α and RANKL/OPG complex showed noteworthy binding affinities which also confirmed the supremacy of CLT due to the additional hydrogen bonding of the hydroxyl groups of the sugar moiety with RANKL/OPG complex. Finally, it is concluded that CLT and GPG from C. procera hinder bone turnover by decreasing osteoclastic bone cells activity and increasing calcium mineralization thus suppressing bone remodeling and preventing bone infirmity in OVX osteoporotic rats directly via binding to RANKL/OPG complex and ER-α and indirectly through elevating level of E2.

Exploring the Role of Hormones and Cytokines in Osteoporosis Development.

The disease of osteoporosis is characterized by impaired bone structure and an increased risk of fractures. There is a significant impact of cytokines and hormones on bone homeostasis and the diagnosis of osteoporosis. As defined by the World Health Organization (WHO), osteoporosis is defined as having a bone mineral density (BMD) that is 2.5 standard deviations (SD) or more below the average for young and healthy women (T score < -2.5 SD). Cytokines and hormones, particularly in the remodeling of bone between osteoclasts and osteoblasts, control the differentiation and activation of bone cells through cytokine networks and signaling pathways like the nuclear factor kappa-B ligand (RANKL)/the receptor of RANKL (RANK)/osteoprotegerin (OPG) axis, while estrogen, parathyroid hormones, testosterone, and calcitonin influence bone density and play significant roles in the treatment of osteoporosis. This review aims to examine the roles of cytokines and hormones in the pathophysiology of osteoporosis, evaluating current diagnostic methods, and highlighting new technologies that could help for early detection and treatment of osteoporosis.

5-Lipoxygenase: The Therapeutically Unexplored Target for Bone Health

Bone fracture is a common orthopedic condition that represents a significant health concern. Bone fracture repair process is a complex process that involves the harmonic and synchronized activity of bone cells. 5-lipoxygenase (5-LOX) is an enzyme responsible for the conversion of arachidonic acid to form leukotrienes. While leukotrienes have an empirical inflammatory role, various evidence suggests that these 5-LOX mediators, by switching the inflammatory environment and altering the activity of bone cells, have a detrimental effect on the bone fracture healing process. Additionally, various evidence suggests that 5-LOX inhibition shows improvement in the overall bone healing process and improves overall bone health. Despite this evidence, the clinical use of 5-LOX inhibitors in bone fracture healing is largely unexplored. The current review aimed to summarize the available evidences and pave the way for future large scale pre-clinical and clinical studies to evaluate the effectiveness of selective 5-LOX inhibitors in bone fracture healing. A comprehensive literature search was conducted in PubMed, Google Scholar, and ScienceDirect to identify relevant articles related to the effect of 5-LOX in bone health. The summary of available scientific evidence highlights that the selective 5-LOX inhibition can modulate the functioning of osteoclasts and osteoblasts, favoring faster bone fracture healing. The observations of this study support the selective 5-LOX inhibition as a potential treatment option that can improve bone fracture healing rate and therefore future clinical studies can be designed to confirm the observations of the current review study.

Osteogenic differentiation by MC3T3-E1 pre-osteoblasts is enhanced more on wet-chemically surface-modified 3D-printed poly-e-caprolactone scaffolds than on plasma-assisted modified scaffolds

3D-Printed poly-є-caprolactone (PCL)-scaffolds are safe for cell support, but their hydrophobicity, bioinertness, and smooth surface limits bioactive/biomimetic performance. This can be overcome by providing biophysicochemical and biomechanical signals using amine (NH2) or carboxyl (COOH)-surface functionalization via wet-chemical treatment or plasma-assisted modification, but the alteration extent and hence bone-cell activity is unknown. We aimed to investigate the influence of NH2 or COOH-surface functionalization via wet-chemical treatment or plasma-assisted modification on biophysicochemical and biomechanical properties of 3D-printed PCL-scaffolds and osteogenic activity. In PCL/NH2 and PCL/COOH scaffolds, only wet-chemical treatment increased void size and surface-roughness, but both treatments reduced water contact angle. Wet-chemical treatment decreased, but plasma-assisted modification increased the elastic modulus. Finite-element modeling revealed that in all scaffolds, maximum von Mises stress under 2% compression-strain did not surpass yield stress for bulk material, indicating excellent mechanical stability and fracture resistance. Wet-chemical treatment and plasma-assisted modification increased pre-osteoblast proliferation, alkaline phosphatase activity, and mineral deposition. Wet-chemical treatment increased Fgf2 mRNA, while both treatments increased Cox2 mRNA. Only wet-chemical treatment increased collagen production. In conclusion, NH2 and COOH-surface functionalization of 3D-printed PCL-scaffolds via wet-chemical treatment was superior to plasma-assisted modification in enhancing osteogenic activity, and is therefore more promising for in vivo bone formation.

The specificities, influencing factors, and medical implications of bone circadian rhythms.

Physiological processes within the human body are regulated in approximately 24-h cycles known as circadian rhythms, serving to adapt to environmental changes. Bone rhythms play pivotal roles in bone development, metabolism, mineralization, and remodeling processes. Bone rhythms exhibit cell specificity, and different cells in bone display various expressions of clock genes. Multiple environmental factors, including light, feeding, exercise, and temperature, affect bone diurnal rhythms through the sympathetic nervous system and various hormones. Disruptions in bone diurnal rhythms contribute to the onset of skeletal disorders such as osteoporosis, osteoarthritis and skeletal hypoplasia. Conversely, these bone diseases can be effectively treated when aimed at the circadian clock in bone cells, including the rhythmic expressions of clock genes and drug targets. In this review, we describe the unique circadian rhythms in physiological activities of various bone cells. Then we summarize the factors synchronizing the diurnal rhythms of bone with the underlying mechanisms. Based on the review, we aim to build an overall understanding of the diurnal rhythms in bone and summarize the new preventive and therapeutic strategies for bone disorders.

Morphometric analysis of rat femurs submitted to the use of dexamethasone and the consumption of curcumin and symbiotics

The aim was to analyze whether the deleterious effects of dexamethasone on bone can be prevented or mitigated by using curcumin and the symbiotic concomitantly. The rats were divided into control (CT), dexamethasone (D), dexamethasone curcumin (DC), dexamethasone symbiotic (DS) and dexamethasone symbiotic/curcumin (DCS) groups. The thickness, area, and area fraction of the bone trabeculae of the femoral head were measured. The CT group showed greater trabecular thickness when compared to the D and DS groups. The thicknesses of the DC and DCS groups were greater than those of the DS group. The area and area fraction were smaller in groups D, DC and DS compared to CT. It can be concluded that curcumin, when consumed in isolation, had a slight effect on maintaining the thickness of trabecular bone. Considering its action on the structuring of the trabecular area, it is not possible to establish a clear relationship between its benefit for bone preservation and its interference with bone cell activity.

Aspects of the dynamics of osteogenesis and bone tissue resorption markers concentrations in elite biathlonists due to the compression specificity of the cyclic training aids used at the stages of the early season

Aim: study the dynamics of osteogenesis and bone resorption markers in elite biathlonists owing to the “compression” specifics of cyclic training aids, mainly used at the stages of the early season of the annual training cycle.Materials and methods: 23 elite biathlonists undergoing centralized training as the members of the Russian national team took part in the study.Results: no changes in the P1NP amounts reaching a reliable level were recorded throughout the early season. The average group osteocalcin amount at the precompetition stage significantly (p &lt; 0,05) increased compared with that measured at the special preliminary stage. Dynamics of β-CrossLaps concentration showed significant (p &lt; 0,05) decrease during the transition from the general preliminary to the special preliminary stage.Conclusion: the degree of intense training activity influence on the activity of bone cells and in turn the response of bone tissue to training loads depend on a set of exercise parameters performed by the athlete, such as duration, intensity, specificity, recovery time and mechanical stress. Optimizing the ratio of cyclic aids with different levels of compression loads during specialized training promotes adaptive changes which protect bone tissue from resorption affected by intense physical exercises. When analyzing the levels of bone metabolism markers for diagnosis and monitoring disorders associated with skeletal overload which could occur high-intensity training loads, an individual approach as well as recognition of the load specifics and parameters performed by an athlete at a specific stage of the training macrocycle are required.

Comparative effects of calcitriol and calcimimetic on bone health in renal insufficiency

AbstractCalcitriol and calcimimetics are used to treat hyperparathyroidism secondary to chronic kidney disease (CKD). Calcitriol administration and the subsequent increase in serum calcium concentration decrease parathyroid hormone (PTH) levels, which should reduce bone remodeling. We have previously reported that, when maintaining a given concentration of PTH, the addition of calcimimetics is associated with an increased bone cell activity. Whether calcitriol administration affects bone cell activity while PTH is maintained constant should be evaluated in an animal model of renal osteodystrophy. The aim of the present study was to compare in CKD PTH‐clamped rats the bone effects of calcitriol and calcimimetic administration. The results show that the administration of calcitriol and calcimimetic at doses that induced a similar reduction in PTH secretion produced dissimilar effects on osteoblast activity in 5/6 nephrectomized (Nx) rats with secondary hyperparathyroidism and in Nx rats with clamped PTH. Remarkably, in both rat models, the administration of calcitriol decreased osteoblastic activity, whereas calcimimetic increased bone cell activity. In vitro, calcitriol supplementation inhibited nuclear translocation of β‐catenin and reduced proliferation, osteogenesis, and mineralization in mesenchymal stem cells differentiated into osteoblasts. In conclusion, besides the action of calcitriol and calcimimetics at parathyroid level, these treatments have specific effects on bone cells that are independent of the PTH level.

Vanadium and strontium co-doped hydroxyapatite enriched polycaprolactone matrices for effective bone tissue engineering: A synergistic approach

Scientific research targeted at enhancing scaffold qualities has increased significantly during the last few decades. This emphasis frequently centres on adding different functions to scaffolds in order to increase their usefulness as instruments in the field of regenerative medicine. This study aims to investigate the efficacy of a multifunctional sustainable polymer scaffold, specifically Polycaprolactone (PCL) embedded with hydroxyapatite co-doped with vanadium and strontium (HVS), for bone tissue engineering applications. Polycaprolactone was used to fabricate the scaffold, while hydroxyapatite co-doped with vanadium and strontium (HVS) served as the nanofiller. A thorough investigation of the physicochemical and biological characteristics of the HVS nanofiller was carried out using cutting-edge techniques including Dynamic Light Scattering (DLS), and X-ray Photoelectron Spectroscopy (XPS) and in vitro cell studies. A cell viability rate of more than 70 % demonstrated that the synthesised nanofiller was cytotoxic, but in an acceptable range. The mechanical, biological, and physicochemical properties of the scaffold were extensively evaluated after the nanofiller was integrated. The water absorption characteristics of scaffold were enhanced by the addition of HVS nanofillers, leading to increased swelling, porosity, and hydrophilicity. These improvements speed up the flow of nutrients and the infiltration of cells into the scaffold. The scaffold has been shown to have important properties that stimulate bone cell activity, including better biodegradability and improved mechanical strength, which increased from 5.30 ± 0.37 to 10.58 ± 0.42 MPa. Further, its considerable antimicrobial qualities, blood-compatible nature, and capacity to promote biomineralization strengthen its appropriateness for usage in biomedical applications. Mainly, enhanced Alkaline phosphatase (ALP) activity, Alizarin Red Staining (ARS) activity, and excellent cell adhesive properties, indicating the outstanding osteogenic potential observed in rat bone marrow-derived stromal cells (rBMSC). These combined attributes highlight the pivotal role of these nanocomposite scaffolds in the field of bone tissue engineering.

A review of mathematical modeling of bone remodeling from a systems biology perspective

Bone remodeling is an essential, delicately balanced physiological process of coordinated activity of bone cells that remove and deposit new bone tissue in the adult skeleton. Due to the complex nature of this process, many mathematical models of bone remodeling have been developed. Each of these models has unique features, but they have underlying patterns. In this review, the authors highlight the important aspects frequently found in mathematical models for bone remodeling and discuss how and why these aspects are included when considering the physiology of the bone basic multicellular unit, which is the term used for the collection of cells responsible for bone remodeling. The review also emphasizes the view of bone remodeling from a systems biology perspective. Understanding the systemic mechanisms involved in remodeling will help provide information on bone pathology associated with aging, endocrine disorders, cancers, and inflammatory conditions and enhance systems pharmacology. Furthermore, some features of the bone remodeling cycle and interactions with other organ systems that have not yet been modeled mathematically are discussed as promising future directions in the field.

The Role of Herbal Medicine in Modulating Bone Homeostasis.

Osteoporosis and other bone diseases are a major public health concern worldwide. Current pharmaceutical treatments for bone disorders have limitations, driving interest in complementary herbal medicines that can help maintain bone health. This review summarizes the scientific evidence for medicinal herbs that modulate bone cell activity and improve bone mass, quality and strength. Herbs with osteogenic, anti-osteoporotic, and anti-osteoclastic effects are discussed, including compounds and mechanisms of action. Additionally, this review examines the challenges and future directions for translational research on herbal medicines for osteoporosis and bone health. While preliminary research indicates beneficial bone bioactivities for various herbs, rigorous clinical trials are still needed to verify therapeutic efficacy and safety. Further studies should also elucidate synergistic combinations, bioavailability of active phytochemicals, and precision approaches to match optimal herbs with specific etiologies of bone disease. Advancing evidence- based herbal medicines may provide novel alternatives for promoting bone homeostasis and treating skeletal disorders.

PTH and the Regulation of Mesenchymal Cells within the Bone Marrow Niche.

Parathyroid hormone (PTH) plays a pivotal role in maintaining calcium homeostasis, largely by modulating bone remodeling processes. Its effects on bone are notably dependent on the duration and frequency of exposure. Specifically, PTH can initiate both bone formation and resorption, with the outcome being influenced by the manner of PTH administration: continuous or intermittent. In continuous administration, PTH tends to promote bone resorption, possibly by regulating certain genes within bone cells. Conversely, intermittent exposure generally favors bone formation, possibly through transient gene activation. PTH's role extends to various aspects of bone cell activity. It directly influences skeletal stem cells, osteoblastic lineage cells, osteocytes, and T cells, playing a critical role in bone generation. Simultaneously, it indirectly affects osteoclast precursor cells and osteoclasts, and has a direct impact on T cells, contributing to its role in bone resorption. Despite these insights, the intricate mechanisms through which PTH acts within the bone marrow niche are not entirely understood. This article reviews the dual roles of PTH-catabolic and anabolic-on bone cells, highlighting the cellular and molecular pathways involved in these processes. The complex interplay of these factors in bone remodeling underscores the need for further investigation to fully comprehend PTH's multifaceted influence on bone health.

Genome-wide association study for bone quality of ducks during the laying period

The cage-rearing model of the modern poultry industry makes the bones of birds, especially egg-laying birds, more vulnerable to fracture, which poses serious damage to the health of birds. Research confirms that genetic material plays an important role in regulating bone growth, development, and remodeling. However, the genetic architecture underlying bone traits is not well understood. The objectives of this study are to identify valuable genes and genetic markers through a genome-wide association study (GWAS) for breeding to improve the duck bone quality. First, we quantified the tibia and femur quality traits of 260 laying ducks. Based on GWAS, a total of 75 SNP loci significantly associated with bone quality traits were identified, and 67 potential candidate genes were annotated. According to gene function analysis, genes P4HA2, WNT3A, and BST1 et al may influence bone quality by regulating bone cell activity, calcium and phosphate metabolism, or bone collagen maturation and cross-linking. Meanwhile, combined with the transcriptome results, we found that HOXB cluster genes are also important in bone growth and development. Therefore, our findings were helpful in further understanding the genetic architecture of the duck bone quality and provided a worthy theoretical basis and technological support to improve duck bone quality by breeding.

Single-cell analysis of immune and stroma cell remodeling in clear cell renal cell carcinoma primary tumors and bone metastatic lesions

BackgroundDespite therapeutic advances, once a cancer has metastasized to the bone, it represents a highly morbid and lethal disease. One third of patients with advanced clear cell renal cell carcinoma (ccRCC) present with bone metastasis at the time of diagnosis. However, the bone metastatic niche in humans, including the immune and stromal microenvironments, has not been well-defined, hindering progress towards identification of therapeutic targets.MethodsWe collected fresh patient samples and performed single-cell transcriptomic profiling of solid metastatic tissue (Bone Met), liquid bone marrow at the vertebral level of spinal cord compression (Involved), and liquid bone marrow from a different vertebral body distant from the tumor site but within the surgical field (Distal), as well as bone marrow from patients undergoing hip replacement surgery (Benign). In addition, we incorporated single-cell data from primary ccRCC tumors (ccRCC Primary) for comparative analysis.ResultsThe bone marrow of metastatic patients is immune-suppressive, featuring increased, exhausted CD8 + cytotoxic T cells, T regulatory cells, and tumor-associated macrophages (TAM) with distinct transcriptional states in metastatic lesions. Bone marrow stroma from tumor samples demonstrated a tumor-associated mesenchymal stromal cell population (TA-MSC) that appears to be supportive of epithelial-to mesenchymal transition (EMT), bone remodeling, and a cancer-associated fibroblast (CAFs) phenotype. This stromal subset is associated with poor progression-free and overall survival and also markedly upregulates bone remodeling through the dysregulation of RANK/RANKL/OPG signaling activity in bone cells, ultimately leading to bone resorption.ConclusionsThese results provide a comprehensive analysis of the bone marrow niche in the setting of human metastatic cancer and highlight potential therapeutic targets for both cell populations and communication channels.

Deletion of the auxiliary α2δ1 voltage sensitive calcium channel subunit in osteocytes and late-stage osteoblasts impairs femur strength and load-induced bone formation in male mice.

Osteocytes sense and respond to mechanical force by controlling the activity of other bone cells. However, the mechanisms by which osteocytes sense mechanical input and transmit biological signals remain unclear. Voltage-sensitive calcium channels (VSCCs) regulate calcium (Ca2+) influx in response to external stimuli. Inhibition or deletion of VSCCs impairs osteogenesis and skeletal responses to mechanical loading. VSCC activity is influenced by its auxiliary subunits, which bind the channel's α1 pore-forming subunit to alter intracellular Ca2+ concentrations. The α2δ1 auxiliary subunit associates with the pore-forming subunit via a glycosylphosphatidylinositol anchor and regulates the channel's calcium-gating kinetics. Knockdown of α2δ1 in osteocytes impairs responses to membrane stretch, and global deletion of α2δ1 in mice results in osteopenia and impaired skeletal responses to loading in vivo. Therefore, we hypothesized that the α2δ1 subunit functions as a mechanotransducer, and its deletion in osteocytes would impair skeletal development and load-induced bone formation. Mice (C57BL/6) with LoxP sequences flanking Cacna2d1, the gene encoding α2δ1, were crossed with mice expressing Cre under the control of the Dmp1 promoter (10kb). Deletion of α2δ1 in osteocytes and late-stage osteoblasts decreased femoral bone quantity (P < .05) by DXA, reduced relative osteoid surface (P < .05), and altered osteoblast and osteocyte regulatory gene expression (P < .01). Cacna2d1f/f, Cre + male mice displayed decreased femoral strength and lower 10-wk cancellous bone in vivo micro-computed tomography measurements at the proximal tibia (P < .01) compared to controls, whereas Cacna2d1f/f, Cre + female mice showed impaired 20-wk cancellous and cortical bone ex vivo micro-computed tomography measurements (P < .05) vs controls. Deletion of α2δ1 in osteocytes and late-stage osteoblasts suppressed load-induced calcium signaling in vivo and decreased anabolic responses to mechanical loading in male mice, demonstrating decreased mechanosensitivity. Collectively, the α2δ1 auxiliary subunit is essential for the regulation of osteoid-formation, femur strength, and load-induced bone formation in male mice.

RNA-binding proteins in bone pathophysiology.

Bone remodelling is a highly regulated process that maintains mineral homeostasis and preserves bone integrity. During this process, intricate communication among all bone cells is required. Indeed, adapt to changing functional situations in the bone, the resorption activity of osteoclasts is tightly balanced with the bone formation activity of osteoblasts. Recent studies have reported that RNA Binding Proteins (RBPs) are involved in bone cell activity regulation. RBPs are critical effectors of gene expression and essential regulators of cell fate decision, due to their ability to bind and regulate the activity of cellular RNAs. Thus, a better understanding of these regulation mechanisms at molecular and cellular levels could generate new knowledge on the pathophysiologic conditions of bone. In this Review, we provide an overview of the basic properties and functions of selected RBPs, focusing on their physiological and pathological roles in the bone.

Protective Effect of Bovine Milk Extracellular Vesicles on Alveolar Bone Loss.

Bovine milk extracellular vesicles (MEVs) have demonstrated therapeutic potential in regulating bone cell activity. However, the outcome of their use on alveolar bone loss has not yet been demonstrated. This study evaluates the effect of oral administration of MEVs on ovariectomized (OVX) mice. There is a reduced height of the alveolar bone crest in OVX mice by MEVs treatment, but the alveolar bone parameters are not altered. OVX mice are then submitted to a force-induced bone remodeling model by orthodontic tooth movement (OTM). MEVs-treated mice have markedly less bone remodeling movement, unlike the untreated OVX mice. Also, OVX mice treated with MEVs show an increased number of osteoblasts and osteocytes associated with higher sclerostin expression and reduce osteoclasts in the alveolar bone. Although the treatment with MEVs in OVX mice does not show differences in root structure in OTM, few odontoclasts are observed in the dental roots of OVX-treated mice. Compared to untreated mice, maxillary and systemic RANKL/OPG ratios are reduced in OVX mice treated with MEVs. Treatment with MEVs results in positive bone cell balance in the alveolar bone and dental roots, indicating its beneficial potential in treating alveolar bone loss in the nutritional context.

Electrospun PAN/PEG Nanofibrous Membrane Embedded with a MgO/gC3N4 Nanocomposite for Effective Bone Regeneration.

Developing biomaterial scaffolds using tissue engineering with physical and chemical surface modification processes can improve the bioactivity and biocompatibility of the materials. The appropriate substrate and site for cell attachment are crucial in cell behavior and biological activities. Therefore, the study aims to develop a conventional electrospun nanofibrous biomaterial using reproducible surface topography, which offers beneficial effects on the cell activities of bone cells. The bioactive MgO/gC3N4 was incorporated on PAN/PEG and fabricated into a nanofibrous membrane using electrospinning. The nanocomposite uniformly distributed on the PAN/PEG nanofiber helps to increase the number of induced pores and reduce the hydrophobicity of PAN. The physiochemical characterization of prepared nanoparticles and nanofibers was carried out using FTIR, X-ray diffraction (XRD), thermogravimetry analysis (TGA), X-ray photoelectron spectroscopy (XPS), and water contact angle measurements. SEM and TEM analyses examined the nanofibrous morphology and the structure of MgO/gC3N4. In vitro studies such as on ALP activity demonstrated the membrane's ability to regenerate new bone and healing capacity. Furthermore, alizarin red staining showed the increasing ability of the cell-cell interaction and calcium content for tissue regeneration. The cytotoxicity of the prepared membrane was about 97.09% of live THP-1 cells on the surface of the MgO/gC3N4@PAN/PEG membrane evaluated using MTT dye staining. The soil burial degradation analysis exhibited that the maximum degradation occurs on the 45th day because of microbial activity. In vitro PBS degradation was observed on the 15th day after the bulk hydrolysis mechanism. Hence, on the basis of the study outcomes, we affirm that the MgO/gC3N4@PAN/PEG nanofibrous membrane can act as a potential bone regenerative substrate.

Effect of Remifentanil on the Osteogenic Activity of Biodegradable Polyhydroxybutyrate Bone Cement in Orthopedic Surgery Model

The objective of this research was to investigate the impacts of Remifentanil on osteogenic activity of biodegradable polyhydroxybutyrate (PHB) bone cement (BPC) in an orthopedic surgery model (OSM). PHB was prepared and characterized. Remifentanil with various concentrations were determined: 0.5, 1.5, 10, 100, and 200 μmol groups, with untreated cells serving as the control (Ctrl) group. Osteoblasts were obtained from bone tissue, and cell proliferation (CP) inhibition was assessed using the MTT assay. Alkaline phosphatase (ALP) activity and insulin-like growth factor-1 (IGF-I) activity were detected using the enzyme-linked immunosorbent assay (ELISA). Expressions of bone-related genes (Runx2, osterix, Bglap, and IBSP) were quantified using fluorescence quantification, and the reactive oxygen species (ROS) levels were measured using a fluorescence microplate reader. The results revealed that different molecular weights (MWs) increased initially and then decreased with increasing radiation time, while diverse temperatures at appropriate reactions yielded higher MWs. Microwave radiation synthesis produced the highest MW of 21.2 × 104 g/mol after a 35-minute reaction. The IGF-I activity in the cell supernatant differed greatly among different groups, with the 100 and 200 μmol groups exhibiting obvious differences with P &lt; 0.05 to the Ctrl group. Marked differences were observed among the 100 and 200 μmol groups and the 0.5, 1.5, and 10 μmol groups, showing P &lt; 0.05. Runx2, osterix, Bglap, and IBSP in the 10, 100, and 200 μmol groups were differed obviously to those in the Ctrl group (P &lt; 0.05). The 10, 100, and 200 μmol groups exhibited remarkable differences based on the Ctrl group (P &lt; 0.05). Remifentanil may negatively impact the osteogenic activity of BPC by inhibiting the activity of bone cells and interfering with the synthesis of extracellular matrix. In conclusion, Remifentanil negatively impacted the osteogenic activity of BPC in the orthopedic surgery model (OSM). Remifentanil may interfere with the bone healing process and further weaken its osteogenic capability.

Whole-body vibration may not affect bone mineral density and bone turnover in persons with chronic spinal cord injury: A preliminary study

Context Spinal-cord injury (SCI) induces bone loss and dramatically increases the risk of fracture. Objectives Determine the effects of whole-body vibration (WBV) on areal bone mineral density (aBMD), whole body composition and bone biological parameters in individuals with chronic-state SCI. Design Randomized study. Setting Centre Neurologique PROPARA. Participants Fourteen subjects were randomly assigned to a WBV or a control group. Interventions WBV (20–45 min, 30–45 Hz, 0.5 g) was performed in verticalized persons twice weekly for 6 months. Outcome Measures aBMD was measured by DXA at baseline and 6 months and bone biological parameters at baseline, 1, 3 and 6 months. Results No significant aBMD change was found in either the WBV or control group after 6 months of follow-up. Similarly, periostin, sclerostin and bone turnover markers remained relatively stable throughout follow-up and no difference in variation was observed within-group and between groups. Except for whole-body fat mass, which showed a significant decrease in the WBV group compared to controls, no difference in changes was observed, whatever the localization for fat and lean body mass. Conclusions During the chronic phase, aBMD and bone remodeling reach a new steady state. However, the DXA technique and the bone markers, including sclerostin and periostin, both of which reflect bone cell activity influenced by mechanical strain, showed that the bone tissue of individuals with SCI was insensitive to 6 months of WBV training at the study dose. Nevertheless, results of this preliminary study that was underpowered need to be confirmed and other modalities of WBV may be more effective in improving aBMD of this population. Trials registration N°IDRCB:2011-A00224–37