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Cartilage, a flexible and smooth connective tissue that envelops the surfaces of synovial joints, relies on chondrocytes for extracellular matrix (ECM) production and the maintenance of its structural and functional integrity. Melatonin (MT), renowned for its anti-inflammatory and antioxidant properties, holds the potential to modulate cartilage regeneration and degradation. Therefore, the present study was devoted to elucidating the mechanism of MT on chondrocytes. The in vivo experiment consisted of three groups: Sham (only the skin tissue was incised), Model (using the anterior cruciate ligament transection (ACLT) method), and MT (30 mg/kg), with sample extraction following 12 weeks of administration. Pathological alterations in articular cartilage, synovium, and subchondral bone were evaluated using Safranin O-fast green staining. Immunohistochemistry (ICH) analysis was employed to assess the expression of matrix degradation-related markers. The levels of serum cytokines were quantified via Enzyme-linked immunosorbent assay (ELISA) assays. In in vitro experiments, primary chondrocytes were divided into Control, Model, MT, negative control, and inhibitor groups. Western blotting (WB) and Quantitative RT-PCR (q-PCR) were used to detect Silent information regulator transcript-1 (SIRT1)/Nuclear factor kappa-B (NF-κB)/Nuclear factor erythroid-2-related factor 2 (Nrf2)/Transforming growth factor-beta (TGF-β)/Bone morphogenetic proteins (BMPs)-related indicators. Immunofluorescence (IF) analysis was employed to examine the status of type II collagen (COL2A1), SIRT1, phosphorylated NF-κB p65 (p-p65), and phosphorylated mothers against decapentaplegic homolog 2 (p-Smad2). In vivo results revealed that the MT group exhibited a relatively smooth cartilage surface, modest chondrocyte loss, mild synovial hyperplasia, and increased subchondral bone thickness. ICH results showed that MT downregulated the expression of components related to matrix degradation. ELISA results showed that MT reduced serum inflammatory cytokine levels. In vitro experiments confirmed that MT upregulated the expression of SIRT1/Nrf2/TGF-β/BMPs while inhibiting the NF-κB pathway and matrix degradation-related components. The introduction of the SIRT1 inhibitor Selisistat (EX527) reversed the effects of MT. Together, these findings suggest that MT has the potential to ameliorate inflammation, inhibit the release of matrix-degrading enzymes, and improve the cartilage condition. This study provides a new theoretical basis for understanding the role of MT in decelerating cartilage degradation and promoting chondrocyte repair in in vivo and in vitro cultured chondrocytes.

Nonylphenol (NP) is a known endocrine-disrupting chemical (EDC) that has been shown to affect bone development in mammals. However, the detrimental impacts of NP on the skeletal growth and development of aquatic species, especially bony fish, remain poorly understood. Bone morphogenic proteins (BMPs), essential for bone formation and osteoblast differentiation, act through the BMP-Smad signaling pathway. In this study, two BMP genes, BMP2 and BMP4, were cloned and characterized in the red crucian carp (Carassius auratus red var.). The full-length cDNAs of BMP2 and BMP4 were 2029 bp and 2095 bp, respectively, encoding polypeptides of 411 and 433 amino acids, and share a typical TGF-β domain with other BMPs. The tissue expression patterns of both genes were identified, showing ubiquitous expression across all studied tissues. Additionally, the exposure of embryos or adult fish to NP stress resulted in a downregulation of BMP2, BMP4, and other genes associated with the BMP-Smad signaling pathway. Moreover, the combined treatment of adult fish with NP and the specific BMP receptor inhibitor significantly reduced these genes’ expression. These findings elucidate the mechanism of NP stress on BMP2 and BMP4, suggesting a role for the BMP-Smad signaling pathway in the response to endocrine-disrupting chemicals in fish.

Non-point source pollution poses a continuous threat to the quality of Great Lakes waters. To abate this problem, the Great Lakes Agricultural Stewardship Initiative (GLASI) was initiated in Ontario, Canada, with the primary aim of reducing phosphorus pollution. Therefore, a case-study analysis of the Wigle Creek watershed, one of the six priority watersheds under the GLASI program, was undertaken to evaluate the effectiveness of various existing and potential future Best Management Practices (BMPs) and to identify BMPs that might aid in mitigating the watershed’s contribution to phosphorus loads reaching Lake Erie. Given the watershed’s very flat topography, hydrological/nutrient modeling proved an extremely challenging exercise. The Soil and Water Assessment Tool (SWAT) model was used in this evaluation. Several digital elevation model (DEM) options were considered to accurately describe the watershed and represent flow conditions. A 30 m resolution DEM, implementing a modified burning in of streams based on ground truthing, was finally employed to develop the SWAT model’s drainage framework. The model was first calibrated for flow, sediment, and phosphorus loads. The calibrated model was used to evaluate the ability of potential BMPs (minimum tillage, no-till, retiring croplands into pasture, retiring croplands into forest, winter wheat cover crop, and vegetative filter strips) to reduce phosphorus loads compared to implemented practice. Converting all croplands into pasture or forest significantly decreased P loads reaching Lake Erie. Comparatively, a winter wheat cover crop had minimal effect on reducing phosphorus loading.

This study was conducted in the Atwood and Tappan Lakes watersheds of the Tuscarawas basin of Ohio. The flow, total nitrogen (TN), and total phosphorus (TP) loadings were monitored with the help of local stakeholders for a few years at various locations of the watershed to develop the Soil and Water Assessment Tool (SWAT). The multi-site SWAT model calibration and validation were accomplished with a reasonable model performance. In the next step, the scenario analysis was conducted in the SWAT model using various BMPs, including vegetative filter strips, grass waterways, fertilizer reduction, crop rotation, and cover crops to evaluate their performance in reducing TN and TP from the watershed. While BMPS in many studies are decided based on researchers’ intuition, these BMPs were selected based on active consultation with the local stakeholders, who were engaged in the reduction of TN and TP loadings from the watersheds. Since the SWAT model calibration for TN and TP was not as good as the hydrologic model calibration, various scenarios of TN and TP reduction using BMPs were investigated for several years using both calibrated and uncalibrated SWAT models. We examined all the BMPs in 12 sub-watersheds of the Atwood and 10 sub-watersheds of the Tappan Lake watershed. The analysis indicated that the management practices of cover crops (rye) in combination with grass waterways with a 10% fertilizer reduction could minimize the TN and TP loading by as much as 88%, without significantly compromising the agricultural yield. However, a 10% fertilizer reduction without any BMPs could reduce TN and TP by just 9%. The cover crop (rye) including 10% fertilizer reduction with grass waterways seemed to be the most effective in reducing TN and TP, whereas the implementation of a filter strip led to a 70% reduction and was the next effective BMPs in reducing TN and TP loadings. In general, TN losses were reduced by 8% to 53%, while TP losses were reduced by 7% to 88%, depending on the BMPs used. By and large, the TN and TP reduction achieved through the calibrated model was not significantly different from the uncalibrated model, even though the reduction using the calibrated model was slightly higher for all scenarios than that of the uncalibrated model. The TN and TP loadings were highly sensitive to cattle grazing. When just 50% of the cattle were permitted to graze, the model predicted that there would be a 40% increase in total nitrogen and a 70% increase in total phosphorus in both watersheds. Our investigation revealed that monitoring the watershed at a small sub-watershed scale and calibrating the SWAT model for nitrogen and phosphorus is delicate.

Subsurface (or tile) drainage improves land productivity by enhancing soil aeration and preventing water-logged conditions. However, the continuous expansion of drained agricultural lands and reliance on synthetic fertilizer in the Midwestern United States have increasingly facilitated nitrate transport from agricultural fields to surface water bodies. Hence, there is a need to implement various agricultural best management practices (BMPs) in order to reduce the adverse water quality impacts resulting from excess nitrate, such as eutrophication and the formation of hypoxic zones. In this study, we used a SWAT+ model to assess the overall impacts on the riverine nitrate load and crop yield in the corn–soybean cropping system based on a combination of different management practices. The corn and soybean yields simulated with the model were found to be in good agreement with the observed yields for both the calibration and validation periods. The long-term simulation over a period of 30 years showed a reduction in the nitrate load of up to 32% without impacting the crop yield. The model results suggest that by reducing the current N application rate by 20% and using a 40:60 split between spring pre-plant and side-dressing N applications combined with cereal rye as a cover crop in corn–soybean rotation, one can potentially reduce nitrate losses without impacting crop yields. This study will help researchers, stakeholders, and farmers to explore and adopt alternative management practices beneficial for offsetting the environmental impacts of agricultural productions on the watershed scale.

This investigation explores the impact of various management practices on nitrate leaching and crop yield in two specific areas in Slovenia. The issue of nitrate leaching from agricultural land is a worldwide threat to drinking water, and despite years of research efforts, universal solutions are still unknown. The two chosen study sites are significant because of their importance for agricultural production and because groundwater aquifers beneath are main sources of drinking water, which makes imposing mitigation measures challenging. One of the areas was reported to be of “bad” status according to the Water Framework Directive criteria, while the other is at risk of reaching this status if nitrate concentrations in groundwater continue to rise. This research used the SWAT model to simulate nitrate leaching and crop yield changes under different agricultural scenarios on different soil types. It aimed to accomplish two objectives: first, to identify parts of the case study areas where the existing combination of soil conditions and agricultural practices enables a high potential for nitrate leaching; second, to identify agricultural practices that decrease nitrate leaching from various soil types while maintaining crop yields in each area. By identifying the most vulnerable locations and the most promising practices, we generated a chart of best management practices for specific soil types as a guide that extension services can use to advise farmers on potential management improvements. The main findings demonstrate that reducing fertilizer application, both organic and inorganic, in areas where the rates exceed crop requirements may not have a significant impact on crop production. However, these reductions often resulted in a noticeable decrease in nitrate exports. The results also showed that soil type is crucially important and should always be considered when evaluating the effects of agricultural management on crop yields and nitrate leaching.

MicroRNAs (miRNAs) are a family of small, single-stranded, and non-protein coding RNAs about 19 to 22 nucleotides in length, that have been reported to have important roles in the control of bone development. MiRNAs have a strong influence on osteoblast differentiation through stages of lineage commitment and maturation, as well as via controlling the activities of osteogenic signal transduction pathways. Generally, miRNAs may modulate cell stemness, proliferation, differentiation, and apoptosis by binding the 3′-untranslated regions (3′-UTRs) of the target genes, which then can subsequently undergo messenger RNA (mRNA) degradation or protein translational repression. MiRNAs manage the gene expression in osteogenic differentiation by regulating multiple signalling cascades and essential transcription factors, including the transforming growth factor-beta (TGF-β)/bone morphogenic protein (BMP), Wingless/Int-1(Wnt)/β-catenin, Notch, and Hedgehog signalling pathways; the Runt-related transcription factor 2 (RUNX2); and osterix (Osx). This shows that miRNAs are essential in regulating diverse osteoblast cell functions. TGF-βs and BMPs transduce signals and exert diverse functions in osteoblastogenesis, skeletal development and bone formation, bone homeostasis, and diseases. Herein, we highlighted the current state of in vitro and in vivo research describing miRNA regulation on the canonical TGF-β/BMP signalling, their effects on osteoblast linage, and understand their mechanism of action for the development of possible therapeutics. In this review, particular attention and comprehensive database searches are focused on related works published between the years 2000 to 2022, using the resources from PubMed, Google Scholar, Scopus, and Web of Science.

The bone morphogenic protein (BMP) family is a member of the TGF-beta superfamily and plays a crucial role during the onset of gut inflammation and arthritis diseases. Recent studies have reported a connection with the gut–joint axis; however, the genetic players are still less explored. Meanwhile, BDMC33 is a newly synthesized anti-inflammatory drug candidate. Therefore, in our present study, we analysed the genome-wide features of the BMP family as well as the role of BMP members in gut-associated arthritis in an inflammatory state and the ability of BDMC33 to attenuate this inflammation. Firstly, genome-wide analyses were performed on the BMP family in the zebrafish genome, employing several in silico techniques. Afterwards, the effects of curcumin analogues on BMP gene expression in zebrafish larvae induced with TNBS (0.78 mg/mL) were determined using real time-qPCR. A total of 38 identified BMP proteins were revealed to be clustered in five major clades and contain TGF beta and TGF beta pro peptide domains. Furthermore, BDMC33 suppressed the expression of four selected BMP genes in the TNBS-induced larvae, where the highest gene suppression was in the BMP2a gene (an eight-fold decrement), followed by BMP7b (four-fold decrement), BMP4 (four-fold decrement), and BMP6 (three-fold decrement). Therefore, this study reveals the role of BMPs in gut-associated arthritis and proves the ability of BDMC33 to act as a potential anti-inflammatory drug for suppressing TNBS-induced BMP genes in zebrafish larvae.

Forest roads often increase runoff and sediment loss, thus greatly impacting hydrological processes in mountainous watersheds. While there has been previous investigation on best management practices (BMPs) to reduce soil erosion from forest roads, few studies have attempted to optimize BMPs based on how much they can decrease sediment connectivity between forest roads and streams. To close this gap in knowledge, we analyzed the spatial relationship between forest roads and streams, presented the spatial distribution of sediment connectivity by integrating the forest roads into the calculation of the index of connectivity (IC), determined how sediment connectivity would respond to additional BMPs through simulating scenarios, and used these data to optimize the BMPs so they would intercept the greatest sediment loads. We found that forest roads and streams in the Xiangchagou watershed in the Dabie Mountain area of China tend to occur within 180 m of each other; however, within the same buffer zones, streams are more often accompanied by forest roads. IC was greatest near road–stream crossings but smaller near streams and forest roads, and it tended to decrease as the buffer distance increased. Furthermore, we found that sediment connectivity was decreased through running a variety of scenarios that used sediment basin and riparian buffers as BMPs between forest roads and streams. Specifically, within this watershed, riparian buffers should be 64 m wide, and there should be 30 sediment basins with a minimum upslope drainage area of 2 ha. At these quantities, the BMPs in this watershed would significantly affect sediment connectivity. By contrast, beyond these thresholds, increasing the width of riparian buffers or the number of sediment basins does not lead to meaningful sediment reductions. In this way, we were able to use the mean change point method to determine the optimal sediment basin quantity (30 with corresponding minimum upslope drainage area of 2 ha) and the optimal riparian buffer width (64 m) for the Xiangchagou watershed. While these results are a first approximation in a novel research area, they can guide forest managers and stakeholders to design and optimize BMPs that control the delivery of eroded sediments associated with forest roads.

Background: Long bone fractures display significant non-union rates, but the exact biological mechanisms implicated in this devastating complication remain unclear. The combination of osteogenetic and angiogenetic factors at the fracture site is an essential prerequisite for successful bone regeneration. The aim of this study is to investigate the results of the clinical implantation of growth factors for intraoperative enhancement of osteogenesis for the treatment of long bone fractures and non-unions. Methods: A systematic literature review search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in the PubMed and Web of Science databases from the date of inception of each database through to 10 January 2022. Specific inclusion and exclusion criteria were applied in order to identify relevant studies reporting on the treatment of upper and lower limb long bone non-unions treated with osteoinductive or cellular factors. Results: Overall, 18 studies met the inclusion criteria and examined the effectiveness of the application of Bone Morphogenetic Proteins-2 and -7 (BMPs), platelet rich plasma (PRP) and mesenchymal stem cells (MSCs). Despite the existence of limitations in the studies analysed (containing mixed groups of open and close fractures, different types of fractures, variability of treatment protocols, different selection criteria and follow-up periods amongst others), their overall effectiveness was found significantly increased in patients who received them compared with the controls (I2 = 60%, 95% CI = 1.59 [0.99–2.54], Z =1.93, p = 0.05). Conclusion: Administration of BMP-2 and -7, PRP and MSCs were considered effective and safe methods in fracture treatment, increasing bone consolidation, reducing time to repair and being linked to satisfactory postoperative functional scores.

Reinforcing the small water cycle is considered to be a holistic approach to both water resource and landscape management. In an agricultural landscape, this can be accomplished by incorporating agricultural conservation practices; their incorporation can reduce surface runoff, increase infiltration, and increase the water holding capacity of a soil. Some typical agricultural conservation practices include: conservation tillage, contour farming, residue incorporation, and reducing field sizes; these efforts aim to keep both water and soil in the landscape. The incorporation of such practices has been extensively studied over the last 40 years. The Soil and Water Assessment Tool (SWAT) was used to model two basins in the Czech Republic (one at the farm-scale and a second at the management-scale) to determine the effects of agriculture conservation practice adoption at each scale. We found that at the farm-scale, contour farming was the most effective practice at reinforcing the small water cycle, followed by residue incorporation. At the management-scale, we found that the widespread incorporation of agricultural conservation practices significantly reinforced the small water cycle, but the relative scale and spatial distribution of their incorporation were not reflected in the SWAT scenario analysis. Individual farmers should be incentivized to adopt agricultural conservation practices, as these practices can have great effects at the farm-scale. At the management-scale, the spatial distribution of agricultural conservation practice adoption was not significant in this study, implying that managers should incentivize any adoption of such practices and that the small water cycle would be reinforced regardless.

During embryogenesis, skeletal development is tightly regulated by locally secreted growth factors that interact with proteoglycans (PGs) in the extracellular matrix (ECM). Bone morphogenetic proteins (BMPs) are multifunctional growth factors that play critical roles in cartilage maturation and bone formation. BMP signals are transduced from plasma membrane receptors to the nucleus through both canonical Smad and noncanonical p38 mitogen-activated protein kinase (MAPK) pathways. BMP signalling is modulated by a variety of endogenous and exogenous molecular mechanisms at different spatiotemporal levels and in both positive and negative manners. As an endogenous example, BMPs undergo extracellular regulation by PGs, which generally regulate the efficiency of ligand-receptor binding. BMP signalling can also be exogenously perturbed by a group of small molecule antagonists, such as dorsomorphin and its derivatives, that selectively bind to and inhibit the intracellular kinase domain of BMP type I receptors. In this review, we present a current understanding of BMPs and PGs functions in cartilage maturation and osteoblast differentiation, highlighting BMP–PG interactions. We also discuss the identification of highly selective small-molecule BMP receptor type I inhibitors. This review aims to shed light on the importance of BMP signalling and PGs in cartilage maturation and bone formation.

State-approved forestry best management practices (BMPs) are a practice or combination of practices that, when properly implemented, effectively prevent or reduce the amount of nonpoint source (NPS) pollution entering waterbodies, such as sediment. Although BMPs are voluntary in most states in the southeastern United States (U.S.), forest landowners operating under the auspices of a forest certification system are required to use BMPs, and forest-certified wood procurement organizations also require loggers who supply them with fiber to use BMPs. Current implementation rates are, on average, 93.6% throughout the southeastern U.S. We conducted a literature review to better understand potential effectiveness of BMPs to conserve aquatic resources and species in the southeastern U.S. Our review focuses on how BMPs reduce NPS pollutants, particularly sediment, fertilizers, and herbicides; how BMPs are monitored throughout the southeastern U.S.; and current implementation rates. Additionally, we discuss how state BMP monitoring programs, coupled with participation in forest certification programs that require routine third-party audits, provide assurance to federal and state agencies that BMPs protect aquatic resources and species. The U.S. Fish and Wildlife Service has recognized that working forests where management activities implement BMPs represent a clear, actionable, and scientifically sound approach for conserving at-risk aquatic species. However, there is a data gap in directly linking BMPs to the conservation of aquatic resources. Given the high diversity of aquatic species in the southeastern U.S., it is important to better understand this potential linkage.

Storm runoff pollutants are among the major sources of surface water impairments, globally. Despite several monitoring programs and guidance on stormwater management practices, there are many streams still impaired by urban runoff. This study evaluates an industry sector’s pollutant discharge characteristics using the self-reported data collected under Tennessee Multi Sector Permit program. The stormwater pollutant discharge characteristics were analyzed from 2014 to 2018 for an industry sector involving twelve facilities in West Tennessee, USA. The data analysis revealed the presence of both organic and inorganic contaminants in stormwater samples collected at all twelve industrial facilities, with the most common metals being magnesium, copper, and aluminum. The principal component analysis (PCA) was applied to better understand the correlation between water quality parameters, their origins, and seasonal variations. Furthermore, the water quality indexes (WQIs) were calculated to evaluate the stormwater quality variations among studied facilities and seasons. The results demonstrated slight variations in stormwater WQIs among the studied facilities ranging from “Bad” to “Medium” quality. The lowest seasonal average WQI was found for spring compared to the other seasons. Certain limitations associated with the self-reported nature of data were identified to inform the decision makers regarding the required future changes.

Characterized by the hardening of arteries, vascular calcification is the deposition of hydroxyapatite crystals in the arterial tissue. Calcification is now understood to be a cell-regulated process involving the phenotypic transition of vascular smooth muscle cells into osteoblast-like cells. There are various pathways of initiation and mechanisms behind vascular calcification, but this literature review highlights the wingless-related integration site (WNT) pathway, along with bone morphogenic proteins (BMPs) and mechanical strain. The process mirrors that of bone formation and remodeling, as an increase in mechanical stress causes osteogenesis. Observing the similarities between the two may aid in the development of a deeper understanding of calcification. Both are thought to be regulated by the WNT signaling cascade and bone morphogenetic protein signaling and can also be activated in response to stress. In a pro-calcific environment, integrins and cadherins of vascular smooth muscle cells respond to a mechanical stimulus, activating cellular signaling pathways, ultimately resulting in gene regulation that promotes calcification of the vascular extracellular matrix (ECM). The endothelium is also thought to contribute to vascular calcification via endothelial to mesenchymal transition, creating greater cell plasticity. Each of these factors contributes to calcification, leading to increased cardiovascular mortality in patients, especially those suffering from other conditions, such as diabetes and kidney failure. Developing a better understanding of the mechanisms behind calcification may lead to the development of a potential treatment in the future.

Congenital heart defects (CHDs) occur with such a frequency that they constitute a significant cause of morbidity and mortality in both children and adults. A significant portion of CHDs can be attributed to aberrant development of the cardiac outflow tract (OFT), and of one of its cellular progenitors known as the cardiac neural crest cells (NCCs). The gene regulatory networks that identify cardiac NCCs as a distinct NCC population are not completely understood. Heart and neural crest derivatives (HAND) bHLH transcription factors play essential roles in NCC morphogenesis. The Hand1PA/OFT enhancer is dependent upon bone morphogenic protein (BMP) signaling in both cranial and cardiac NCCs. The Hand1PA/OFT enhancer is directly repressed by the endothelin-induced transcription factors DLX5 and DLX6 in cranial but not cardiac NCCs. This transcriptional distinction offers the unique opportunity to interrogate NCC specification, and to understand why, despite similarities, cranial NCC fate determination is so diverse. We generated a conditionally active transgene that can ectopically express DLX5 within the developing mouse embryo in a Cre-recombinase-dependent manner. Ectopic DLX5 expression represses cranial NCC Hand1PA/OFT-lacZ reporter expression more effectively than cardiac NCC reporter expression. Ectopic DLX5 expression induces broad domains of NCC cell death within the cranial pharyngeal arches, but minimal cell death in cardiac NCC populations. This study shows that transcription control of NCC gene regulatory programs is influenced by their initial specification at the dorsal neural tube.

Best management practices (BMPs) are an effective way to control water pollution. However, identification of the optimal distribution and cost-effect of BMPs provides a great challenge for watershed policy makers. In this paper, a semi-distributed, low-data, and robust watershed model, the Revised Generalized Watershed Loading Function (RGWLF), is improved by adding the pollutant attenuation process in the river channel and a bank filter strips reduction function. Three types of pollution control measures—point source wastewater treatment, bank filter strips, and converting farmland to forest—are considered, and the cost of each measure is determined. Furthermore, the RGWLF watershed model is coupled with a widely recognized multi-objective optimization algorithm, the non-dominated sorting genetic algorithm II (NSGAII), the combination of which is applied in the Luanhe watershed to search for spatial BMPs for dissolved nitrogen (DisN). Fifty scenarios were finally selected from numerous possibilities and the results indicate that, at a minimum cost of 9.09 × 107 yuan, the DisN load is 3.1 × 107 kg and, at a maximum cost of 1.77 × 108 yuan, the total dissolved nitrogen load is 1.31 × 107 kg; with the no-measures scenario, the DisN load is 4.05 × 107 kg. This BMP optimization model system could assist decision-makers in determining a scientifically comprehensive plan to realize cost-effective goals for the watershed.

Trauma and disease frequently result in fractures or critical sized bone defects and their management at times necessitates bone grafting. The process of bone healing or regeneration involves intricate network of molecules including bone morphogenetic proteins (BMPs). BMPs belong to a larger superfamily of proteins and are very promising and intensively studied for in the enhancement of bone healing. More than 20 types of BMPs have been identified but only a subset of BMPs can induce de novo bone formation. Many research groups have shown that BMPs can induce differentiation of mesenchymal stem cells and stem cells into osteogenic cells which are capable of producing bone. This review introduces BMPs and discusses current advances in preclinical and clinical application of utilizing various biomaterial carriers for local delivery of BMPs to enhance bone regeneration.

The Transforming Growth Factor beta (TGFβ) and Bone Morphogenic Protein (BMP) pathways intersect at multiple signaling hubs and cooperatively or counteractively participate to bring about cellular processes which are critical not only for tissue morphogenesis and organogenesis during development, but also for adult tissue homeostasis. The proper functioning of the TGFβ/BMP pathway depends on its communication with other signaling pathways and any deregulation leads to developmental defects or diseases, including fibrosis and cancer. In this review we explore the cellular and physio-pathological contexts in which the synergism or antagonism between the TGFβ and BMP pathways are crucial determinants for the normal developmental processes, as well as the progression of fibrosis and malignancies.

The Long-Term Hydrology Impact Assessment (L-THIA) model has been used as a screening evaluation tool in assessing not only urbanization, but also land-use changes on hydrology in many countries. However, L-THIA has limitations due to the number of available land-use data that can represent a watershed and the land surface complexity causing uncertainties in manually calibrating various input parameters of L-THIA. Thus, we modified the L-THIA model so that could use various (twenty three) land-use categories by considering various hydrologic responses and nonpoint source (NPS) pollutant loads. Then, we developed a web-based auto-calibration module by integrating a Genetic-Algorithm (GA) into the L-THIA 2012 that can automatically calibrate Curve Numbers (CNs) for direct runoff estimations. Based on the optimized CNs and Even Mean Concentrations (EMCs), our approach calibrated surface runoff and nonpoint source (NPS) pollution loads by minimizing the differences between the observed and simulated data. Here, we used default EMCs of biochemical oxygen demand (BOD), total nitrogen (TN), and total phosphorus-TP (as the default values to L-THIA) collected at various local regions in South Korea corresponding to the classifications of different rainfall intensities and land use for improving predicted NPS pollutions. For assessing the model performance, the Yeoju-Gun and Icheon-Si sites in South Korea were selected. The calibrated runoff and NPS (BOD, TN, and TP) pollutions matched the observations with the correlation (R2: 0.908 for runoff and R2: 0.882–0.981 for NPS) and Nash-Sutcliffe Efficiency (NSE: 0.794 for runoff and NSE: 0.882–0.981 for NPS) for the sites. We also compared the NPS pollution differences between the calibrated and averaged (default) EMCs. The calibrated TN and TP (only for Yeoju-Gun) EMCs-based pollution loads identified well with the measured data at the study sites, but the BOD loads with the averaged EMCs were slightly better than those of the calibrated EMCs. The TP loads for the Yeoju-Gun site were usually comparable to the measured data, but the TP loads of the Icheon-Si site had uncertainties. These findings indicate that the web-based auto-calibration module integrated with L-THIA 2012 could calibrate not only the surface runoff and NPS pollutions well, but also provide easy access to users across the world. Thus, our approach could be useful in providing a tool for Best Management Practices (BMPs) for policy/decision-makers.

The dense highland field area in the upstream region of the Lake Soyang watershed is subject to excessive soil erosion during the wet season. In this study, stormwater runoff from the Lake Soyang watershed was monitored during four rainfall events at 10 locations throughout 2016. The maximum SS concentration at Naedongcheon, which is located in the upper part of the Soyang River, reached 4598 mg/L. The event mean concentration (EMC) of SS loads in Naedongcheon ranged from 82.2 mg/L to 926.3 mg/L. We found that, although the first flush events were usually concentrated in highly paved urban areas, a first flush occurred in the agricultural area of the dense highland field region. The first flush phenomenon was identified by a dimensionless cumulative runoff mass and volume curve (M(V) curve), and the intensity of the first flush was analyzed by the coefficient of the nonlinear regression model and the FF30 and FF25 values (the fraction of pollution load transported by the first 30% and 25% of runoff, respectively). Nonlinear regression models using the power function were applied to fit the M(V) curve, the FF30 values were inversely proportional to the coefficient a of the regression model. A long-term seasonal trend decomposition for monthly turbidity and precipitation was performed for the Lake Soyang. Long-term turbidity trend was approximately coincident with the trend in long-term precipitation. In addition, the present status of the best management practices (BMPs) in the upper part of the Soyang River basin was investigated, and a survey of the management and operation of the BMPs was conducted for selected farmers.

This article presents a methodology to optimize the integration of local scale drainage measures in catchment modelling. The methodology enables to zoom into the processes (physically, spatially and temporally) where detailed physical based computation is required and to zoom out where lumped conceptualized approaches are applied. It allows the definition of parameters and computation procedures on different spatial and temporal scales. Three methods are developed to integrate features of local scale drainage measures in catchment modelling: (1) different types of local drainage measures are spatially integrated in catchment modelling by a data mapping; (2) interlinked drainage features between data objects are enabled on the meso, local and micro scale; (3) a method for modelling multiple interlinked layers on the micro scale is developed. For the computation of flow routing on the meso scale, the results of the local scale measures are aggregated according to their contributing inlet in the network structure. The implementation of the methods is realized in a semi-distributed rainfall-runoff model. The implemented micro scale approach is validated with a laboratory physical model to confirm the credibility of the model. A study of a river catchment of 88 km2 illustrated the applicability of the model on the regional scale.

The selection of stormwater Best Management Practices (BMPs) for mitigating the effects of urbanization on the hydrological cycle could be a complex process due to conflicting stakeholder views, and varying levels of performance of BMPs across a range of criteria (runoff reduction, erosion control, etc.). Part 1 of this article proposed a methodology based on the application of multi-criteria decision aid (MCDA) methods, which was tested here on a residential stormwater network in the Montreal area. The case study considered green roofs, rain gardens, rain barrels and pervious pavement over a range of economic, social, and water quality and quantity criteria by applying 4 MCDA methods under three different stakeholder views. The results indicated Elimination et Choix Traduisant la Réalité (ELECTRE) III to be the most appropriate method for the methodology, presenting flexibility concerning threshold values, criteria weights, and showing shared top choices across stakeholders (rain gardens, and rain gardens in combination with pervious pavement). The methodology shows potential for more formal applications and research opportunities. Future work may lie in the inclusion of multiple objective optimization, better stakeholder engagement, estimation of economic benefits, water quality modeling, long-term hydrological simulations, and estimating real BMP pollutant removal rates.

The implementation of stormwater Best Management Practices (BMPs) could help re-establish the natural hydrological cycle of watersheds after urbanization, with each BMP presenting a different performance across a range of criteria (flood prevention, pollutant removal, etc.). Additionally, conflicting views from the relevant stakeholders may arise, resulting in a complex selection process. This paper proposes a methodology for BMP selection based on the application of multi-criteria decision aid (MCDA) methods, integrating multiple stakeholder priorities and BMP combinations. First, in the problem definition, the MCDA methods, relevant criteria and design guidelines are selected. Next, information from the preliminary analysis of the watershed is used to obtain a list of relevant BMPs. The third step comprises the watershed modeling and analysis of the BMP alternatives to obtain performance values across purely objective criteria. Afterwards, a stakeholder analysis based on survey applications is carried out to obtain social performance values and criteria priorities. Then, the MCDA methods are applied to obtain the final BMP rankings. The last step considers the sensitivity analysis and rank comparisons in order to draw the final conclusions and recommendations. Future improvements to the methodology could explore inclusion of multiple objective analysis, and alternative means for obtaining social performance values.

Background: Long bone fractures display significant non-union rates, but the exact biological mechanisms implicated in this devastating complication remain unclear. The combination of osteogenetic and angiogenetic factors at the fracture site is an essential prerequisite for successful bone regeneration. The aim of this study is to investigate the results of the clinical implantation of growth factors for intraoperative enhancement of osteogenesis for the treatment of long bone fractures and non-unions., Methods: A systematic literature review search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in the PubMed and Web of Science databases from the date of inception of each database through to 10 January 2022. Specific inclusion and exclusion criteria were applied in order to identify relevant studies reporting on the treatment of upper and lower limb long bone non-unions treated with osteoinductive or cellular factors., Results: Overall, 18 studies met the inclusion criteria and examined the effectiveness of the application of Bone Morphogenetic Proteins-2 and -7 (BMPs), platelet rich plasma (PRP) and mesenchymal stem cells (MSCs). Despite the existence of limitations in the studies analysed (containing mixed groups of open and close fractures, different types of fractures, variability of treatment protocols, different selection criteria and follow-up periods amongst others), their overall effectiveness was found significantly increased in patients who received them compared with the controls (I 2 = 60%, 95% CI = 1.59 [0.99-2.54], Z =1.93, p = 0.05)., Conclusion: Administration of BMP-2 and -7, PRP and MSCs were considered effective and safe methods in fracture treatment, increasing bone consolidation, reducing time to repair and being linked to satisfactory postoperative functional scores.

During embryogenesis, skeletal development is tightly regulated by locally secreted growth factors that interact with proteoglycans (PGs) in the extracellular matrix (ECM). Bone morphogenetic proteins (BMPs) are multifunctional growth factors that play critical roles in cartilage maturation and bone formation. BMP signals are transduced from plasma membrane receptors to the nucleus through both canonical Smad and noncanonical p38 mitogen-activated protein kinase (MAPK) pathways. BMP signalling is modulated by a variety of endogenous and exogenous molecular mechanisms at different spatiotemporal levels and in both positive and negative manners. As an endogenous example, BMPs undergo extracellular regulation by PGs, which generally regulate the efficiency of ligand-receptor binding. BMP signalling can also be exogenously perturbed by a group of small molecule antagonists, such as dorsomorphin and its derivatives, that selectively bind to and inhibit the intracellular kinase domain of BMP type I receptors. In this review, we present a current understanding of BMPs and PGs functions in cartilage maturation and osteoblast differentiation, highlighting BMP-PG interactions. We also discuss the identification of highly selective small-molecule BMP receptor type I inhibitors. This review aims to shed light on the importance of BMP signalling and PGs in cartilage maturation and bone formation.

Characterized by the hardening of arteries, vascular calcification is the deposition of hydroxyapatite crystals in the arterial tissue. Calcification is now understood to be a cell-regulated process involving the phenotypic transition of vascular smooth muscle cells into osteoblast-like cells. There are various pathways of initiation and mechanisms behind vascular calcification, but this literature review highlights the wingless-related integration site (WNT) pathway, along with bone morphogenic proteins (BMPs) and mechanical strain. The process mirrors that of bone formation and remodeling, as an increase in mechanical stress causes osteogenesis. Observing the similarities between the two may aid in the development of a deeper understanding of calcification. Both are thought to be regulated by the WNT signaling cascade and bone morphogenetic protein signaling and can also be activated in response to stress. In a pro-calcific environment, integrins and cadherins of vascular smooth muscle cells respond to a mechanical stimulus, activating cellular signaling pathways, ultimately resulting in gene regulation that promotes calcification of the vascular extracellular matrix (ECM). The endothelium is also thought to contribute to vascular calcification via endothelial to mesenchymal transition, creating greater cell plasticity. Each of these factors contributes to calcification, leading to increased cardiovascular mortality in patients, especially those suffering from other conditions, such as diabetes and kidney failure. Developing a better understanding of the mechanisms behind calcification may lead to the development of a potential treatment in the future.

Congenital heart defects (CHDs) occur with such a frequency that they constitute a significant cause of morbidity and mortality in both children and adults. A significant portion of CHDs can be attributed to aberrant development of the cardiac outflow tract (OFT), and of one of its cellular progenitors known as the cardiac neural crest cells (NCCs). The gene regulatory networks that identify cardiac NCCs as a distinct NCC population are not completely understood. Heart and neural crest derivatives (HAND) bHLH transcription factors play essential roles in NCC morphogenesis. The Hand1 PA/OFT enhancer is dependent upon bone morphogenic protein (BMP) signaling in both cranial and cardiac NCCs. The Hand1 PA/OFT enhancer is directly repressed by the endothelin-induced transcription factors DLX5 and DLX6 in cranial but not cardiac NCCs. This transcriptional distinction offers the unique opportunity to interrogate NCC specification, and to understand why, despite similarities, cranial NCC fate determination is so diverse. We generated a conditionally active transgene that can ectopically express DLX5 within the developing mouse embryo in a Cre-recombinase-dependent manner. Ectopic DLX5 expression represses cranial NCC Hand1 PA/ OFT - lacZ reporter expression more effectively than cardiac NCC reporter expression. Ectopic DLX5 expression induces broad domains of NCC cell death within the cranial pharyngeal arches, but minimal cell death in cardiac NCC populations. This study shows that transcription control of NCC gene regulatory programs is influenced by their initial specification at the dorsal neural tube.