Wireless Pressure Sensor Assisted Orthopedic Nursing Effectiveness Evaluation

This paper combines flexible pressure sensing technology, wireless sensor network, and cloud platform technology to design and manufacture a medical miniature pressure sensor and its supporting system. The problem of noninvasive monitoring of the syndrome encountered in the clinic is used for real-time monitoring and auxiliary diagnosis of the disease. Different from the current clinical use of “puncture” to measure intrafascial pressure, this system focuses on the noninvasive monitoring of compartment syndrome, using medical tape to paste a flexible microsensing unit on the injured area. The flexible sensor unit can measure the pressure here in real time and then can know the pressure in the fascia chamber. The flexible pressure sensor unit combines with the subsequent flexible circuit to send the measured data to the data in real time through wireless communication. The data aggregation node transmits the collected data to the upper computer through serial communication, and the upper computer software processes and stores the data and uploads it to the cloud server. In this experiment, it was observed that the concentrations of Ca and P showed the same fluctuating trend. With the gradual progress of the stretch, the concentrations of Ca and P increased with the increase in time, reaching approximately at the end of the extension. The peak value indicates that the osteoclast activity is enhanced at this time, the bone matrix is largely destroyed, and the Ca and P in the matrix are released into the serum in a large amount, thereby increasing the serum concentration. After the distraction ceases, it enters the healing period of the callus. At this time, the concentrations of Ca and P decrease with the increase in time and gradually reach a stable level, indicating that the osteoblast activity is enhanced at this time, the bone matrix begins to rebuild, and the Ca and P gradually increase. The deposited bone matrix gradually forms new bone and finally reaches a balance. Since the speed of extension in each experimental group is inconsistent, the time required to reach the same extension length is also inconsistent, so that the peak time is also inconsistent. After plotting the stress difference ( △ F ) before and after stretching against time and speed, it is found that the relationship is linear. However, these two variables affect △ F at the same time, so they cannot be isolated. Based on this, this subject uses multiple regression equations to fit the three relationships of stress difference ( △ F ), time, and speed. In the process of distraction osteogenesis, with each distraction, the bone stress presents a trend from high to low. And as the stretch progresses, the measured stress value increases linearly at the same time point every day.

The phytochemical plumbagin reciprocally modulates osteoblasts and osteoclasts

Bone metabolism is essential for maintaining bone mineral density and bone strength through a balance between bone formation and bone resorption. Bone formation is associated with osteoblast activity whereas bone resorption is linked to osteoclast differentiation. Osteoblast progenitors give rise to the formation of mature osteoblasts whereas monocytes are the precursors for multi-nucleated osteoclasts. Chronic inflammation, auto-inflammation, hormonal changes or adiposity have the potential to disturb the balance between bone formation and bone loss. Several plant-derived components are described to modulate bone metabolism and alleviate osteoporosis by enhancing bone formation and inhibiting bone resorption. The plant-derived naphthoquinone plumbagin is a bioactive compound that can be isolated from the roots of the Plumbago genus. It has been used as traditional medicine for treating infectious diseases, rheumatoid arthritis and dermatological diseases. Reportedly, plumbagin exerts its biological activities primarily through induction of reactive oxygen species and triggers osteoblast-mediated bone formation. It is plausible that plumbagin’s reciprocal actions – inhibiting or inducing death in osteoclasts but promoting survival or growth of osteoblasts – are a function of the synergy with bone-metabolizing hormones calcitonin, Parathormone and vitamin D. Herein, we develop a framework for plausible molecular modus operandi of plumbagin in bone metabolism.

Low Frequency Electromagnetic Fields Might Increase the Effect of Enamel Matrix Derivative on Periodontal Tissues

Periodontal regeneration is a complex goal, which is commonly pursued with a combination of surgical techniques, biomaterials, and bioactive compounds. One such compound is enamel matrix derivative (EMD), a medical substance that is extracted from porcine tooth germs and which contains several protein fractions with BMP- and TGF-β-like action. Activation of TGF-β signaling is required for EMD activity on cells and tissues, and a growing body of evidence indicates that EMD largely relies on this pathway. As low frequency electromagnetic fields (EMFs) have long been investigated as a tool to promote bone formation and osteoblast activity, and because recent studies have reported that the effects of EMFs on cells require primary cilia, by modulating the presence of membrane-bound receptors (e.g., for BMP) or signal mediators, it can be hypothesized that the application of EMFs may increase cell sensitivity to EMD: as TGFBR receptors have also been identified on primary cilia, EMFs could make cells more responsive to EMD by inducing the display of a higher number of receptors on the cellular membrane.

Probiotics and Isoflavones as a Promising Therapeutic for Calcium Status and Bone Health: A Narrative Review

Probiotics have potential clinical effects for treating and preventing osteoporosis. Meanwhile, isoflavones have attracted much attention due to their ability to prevent postmenopausal symptoms. Research has established that probiotics and isoflavones can regulate hormones, immune cells, and the gastrointestinal system, acting as links in the gut–bone axis. However, combining the effects of probiotics and isoflavones on calcium status and bone health is a more novel and a still-evolving research area. Lactobacillus and Bifidobacterium are the foremost strains that influence bone health to a significant extent. Among the isoflavones, daidzein, genistein, and the metabolites of genistein (such as equol) stimulate bone formation. It can be concluded that probiotics and isoflavones promote bone health by regulating calcium uptake, gut microbiota, and various metabolic pathways that are associated with osteoblast activity and bone formation. Nevertheless, further experiments of probiotics and isoflavones are still necessary to confirm the association between calcium bioavailability and bone health.

Connexin Hemichannels with Prostaglandin Release in Anabolic Function of Bone to Mechanical Loading

Mechanical stimulation, such as physical exercise, is essential for bone formation and health. Here, we demonstrate the critical role of osteocytic Cx43 hemichannels in anabolic function of bone in response to mechanical loading. Two transgenic mouse models, R76W and Δ130-136, expressing dominant-negative Cx43 mutants in osteocytes were adopted. Mechanical loading of tibial bone increased cortical bone mass and mechanical properties in wild-type and gap junction-impaired R76W mice through increased PGE2, endosteal osteoblast activity, and decreased sclerostin. These anabolic responses were impeded in gap junction/hemichannel-impaired Δ130-136 mice and accompanied by increased endosteal osteoclast activity. Specific inhibition of Cx43 hemichannels by Cx43(M1) antibody suppressed PGE2 secretion and impeded loading-induced endosteal osteoblast activity, bone formation and anabolic gene expression. PGE2 administration rescued the osteogenic response to mechanical loading impeded by impaired hemichannels. Together, osteocytic Cx43 hemichannels could be a potential new therapeutic target for treating bone loss and osteoporosis.

Osteopontin and Vascular Endothelial Growth Factor-Immunoreactivity in Critical Bone Defects Matrix Production: A Nano-Hydroxyapatite/Beta-Tricalcium Phosphate and Xenogeneic Hydroxyapatite Comparison

The development of new bone substitutes has become an area of great interest in materials science. In fact, hydroxyapatite is the most commonly used biomaterial in defects that require bone reconstruction, and that is certainly why the discovery of new products with its formulation has been increasing continuously. The aim of this study was to analyze the biological behavior of a xenogeneic hydroxyapatite widely disclosed in the literature and a synthetic nano-hydroxyapatite/Beta tricalcium phosphate in critical defects in the calvaria of Wistar rats. For this, the groups were divided as follows: 24 adult male Wistar rats were used, weighing between 300 and 350 g, in three groups with eight animals each. In the CTRL group (control), only the clot was kept, without material insertion; in the Bioss group (bovine hydroxyapatite), Bio Oss®—Gleistlich® was introduced; and in the Blue Bone group (REG), the defect was filled in with synthetic nano-hydroxyapatite associated with betatriphosphate of calcium, Blue Bone®—Regener®. According to the results in Goldner’s Trichromics, we can observe a higher percentage of newly formed bone matrix in the REG group than in the CTRL and Bioss groups; in the VEGF, we had a more adequate cell modulation for blood vessel formation in the Blue Bone group (REG) compared to the Bioss and CTRL groups, while in osteopontin, a higher percentage of bone formation was observed in the Blue Bone group (REG) and Bioss group when compared to the CTRL group. We conclude that bone formation, mitosis-inducing cell modulation and main osteoblast activity were higher in the Blue Bone group (REG) than in the CTRL and Bioss groups.

Epo/EpoR signaling in osteoprogenitor cells is essential for bone homeostasis and Epo-induced bone loss

High erythropoietin (Epo) levels are detrimental to bone health in adult organisms. Adult mice receiving high doses of Epo lose bone mass due to suppressed bone formation and increased bone resorption. In humans, high serum Epo levels are linked to fractures in elderly men. Our earlier studies indicated that Epo modulates osteoblast activity; however, direct evidence that Epo acts via its receptor (EpoR) on osteoblasts in vivo is still missing. Here, we created mice lacking EpoR in osteoprogenitor cells to specifically address this gap. Deletion of EpoR in osteoprogenitors (EpoR:Osx-cre, cKO) starting at 5 weeks of age did not alter red blood cell parameters but increased vertebral bone volume by 25% in 12-week-old female mice. This was associated with low bone turnover. Histological (osteoblast number, bone formation rate) and serum (P1NP, osteocalcin) bone formation parameters were all reduced, as were the number of osteoclasts and TRAP serum level. Differentiation of osteoblast precursors isolated from cKO versus control mice resulted in lower expression of osteoblast marker genes including Runx2, Alp, and Col1a1 on day 21, whereas the mineralization capacity was similar. Moreover, the RANKL/OPG ratio, which determines the osteoclast-supporting potential of osteoblasts, was substantially decreased by 50%. Similarly, coculturing cKO osteoblasts with control or cKO osteoclast precursors produced significantly fewer osteoclasts than coculture with control osteoblasts. Finally, exposing female mice to Epo pumps (10 U·d−1) for 4 weeks resulted in trabecular bone loss (−25%) and increased osteoclast numbers (1.7-fold) in control mice only, not in cKO mice. Our data show that EpoR in osteoprogenitors is essential in regulating osteoblast function and osteoblast-mediated osteoclastogenesis via the RANKL/OPG axis. Thus, osteogenic Epo/EpoR signaling controls bone mass maintenance and contributes to Epo-induced bone loss.

Exosome: Function and Application in Inflammatory Bone Diseases

In the skeletal system, inflammation is closely associated with many skeletal disorders, including periprosthetic osteolysis (bone loss around orthopedic implants), osteoporosis, and rheumatoid arthritis. These diseases, referred to as inflammatory bone diseases, are caused by various oxidative stress factors in the body, resulting in long-term chronic inflammatory processes and eventually causing disturbances in bone metabolism, increased osteoclast activity, and decreased osteoblast activity, thereby leading to osteolysis. Inflammatory bone diseases caused by nonbacterial factors include inflammation- and bone resorption-related processes. A growing number of studies show that exosomes play an essential role in developing and progressing inflammatory bone diseases. Mechanistically, exosomes are involved in the onset and progression of inflammatory bone disease and promote inflammatory osteolysis, but specific types of exosomes are also involved in inhibiting this process. Exosomal regulation of the NF-κB signaling pathway affects macrophage polarization and regulates inflammatory responses. The inflammatory response further causes alterations in cytokine and exosome secretion. These signals regulate osteoclast differentiation through the receptor activator of the nuclear factor-kappaB ligand pathway and affect osteoblast activity through the Wnt pathway and the transcription factor Runx2, thereby influencing bone metabolism. Overall, enhanced bone resorption dominates the overall mechanism, and over time, this imbalance leads to chronic osteolysis. Understanding the role of exosomes may provide new perspectives on their influence on bone metabolism in inflammatory bone diseases. At the same time, exosomes have a promising future in diagnosing and treating inflammatory bone disease due to their unique properties.

Reelin depletion alleviates multiple myeloma bone disease by promoting osteogenesis and inhibiting osteolysis

Extracellular matrix glycoprotein Reelin is associated with tumor metastasis and prognosis in various malignancies. However, its effects on multiple myeloma (MM) are not fully understood. Here, we investigated the regulatory effects of Reelin on MM and its underlying pathogenic mechanisms. Lentivirus plasmid containing short hairpin RNA targeting Reelin (LV3-Reln) was transfected into SP2/0 cells to knockdown Reelin expression. Flow cytometry assay analyzed cell cycle and apoptosis while Transwell assay evaluated invasiveness. BALB/c mice were inoculated with LV3-Reln-transfected SP2/0 cells to establish MM model. Primary myeloma cells and osteoblasts/osteoclast were isolated from tumor tissue and limb long bones respectively. ELISA examined serum biomarkers and immunohistochemistry detected immunoglobulin light chain expression. Morphological changes and osteoclast/osteoblast differentiation were observed by histological staining. mRNA and proteins expression were determined by qPCR and WB. In vitro studies showed that Reelin depletion regulated osteolysis and osteogenesis balance, cell cycle, invasiveness, and apoptosis in SP2/0 cells. In LV3-Reln mice, tumor growth and invasiveness were suppressed, meanwhile, reduced osteoclast activation and enhanced osteoblast activity were observed. Reelin knockdown alleviated extramedullary morbidity and inhibited spleen immune cell apoptosis by down-regulating CDK5, IL-10, and Cyto-C expression. Furthermore, reduced Reelin expression restrained osteoclast differentiation while promoted osteogenesis in the bone of LV3-Reln mice. This was further supported by down-regulation of osteolytic specific mRNAs and proteins (Trap, Mmp9, Ctsk, Clcn7) and up-regulation of osteogenic specific ones (COL-1, Runx2, β-Catenin). Reelin exerted important impacts on myeloma development through rebalancing osteolysis and osteogenesis, thus might be a potential therapeutic target for MM.

Physiologic Mechanical Stress Directly Induces Bone Formation by Activating Glucose Transporter 1 (Glut 1) in Osteoblasts, Inducing Signaling via NAD+-Dependent Deacetylase (Sirtuin 1) and Runt-Related Transcription Factor 2 (Runx2)

Mechanical stress is an important factor affecting bone tissue homeostasis. We focused on the interactions among mechanical stress, glucose uptake via glucose transporter 1 (Glut1), and the cellular energy sensor sirtuin 1 (SIRT1) in osteoblast energy metabolism, since it has been recognized that SIRT1, an NAD+-dependent deacetylase, may function as a master regulator of the mechanical stress response as well as of cellular energy metabolism (glucose metabolism). In addition, it has already been demonstrated that SIRT1 regulates the activity of the osteogenic transcription factor runt-related transcription factor 2 (Runx2). The effects of mechanical loading on cellular activities and the expressions of Glut1, SIRT1, and Runx2 were evaluated in osteoblasts and chondrocytes in a 3D cell–collagen sponge construct. Compressive mechanical loading increased osteoblast activity. Mechanical loading also significantly increased the expression of Glut1, significantly decreased the expression of SIRT1, and significantly increased the expression of Runx2 in osteoblasts in comparison with non-loaded osteoblasts. Incubation with a Glut1 inhibitor blocked mechanical stress-induced changes in SIRT1 and Runx2 in osteoblasts. In contrast with osteoblasts, the expressions of Glut1, SIRT1, and Runx2 in chondrocytes were not affected by loading. Our present study indicated that mechanical stress induced the upregulation of Glut1 following the downregulation of SIRT1 and the upregulation of Runx2 in osteoblasts but not in chondrocytes. Since SIRT1 is known to negatively regulate Runx2 activity, a mechanical stress-induced downregulation of SIRT1 may lead to the upregulation of Runx2, resulting in osteoblast differentiation. Incubation with a Glut1 inhibitor the blocked mechanical stress-induced downregulation of SIRT1 following the upregulation of Runx2, suggesting that Glut1 is necessary to mediate the responses of SIRT1 and Runx2 to mechanical loading in osteoblasts.