Yu-Wen Su's research while affiliated with University of South Australia and other places

Publications (32)

Article
Full-text available
Intensive cancer chemotherapy is well known to cause bone vasculature disfunction and damage, but the mechanism is poorly understood and there is a lack of treatment. Using a rat model of methotrexate (MTX) chemotherapy (five once-daily dosses at 0.75 mg/kg), this study investigated the roles of the Notch2 signalling pathway in MTX chemotherapy-ind...
Article
Full-text available
Methotrexate (MTX) is a commonly used antimetabolite in cancer treatment. Its intensive use is linked with skeletal adverse effects such as reduced bone formation and bone loss, and yet little information is available on molecular mechanisms underlying MTX-induced impaired bone formation. This study investigated the effects of MTX treatment at a cl...
Article
Methotrexate (MTX) is a commonly used anti-metabolite in cancer treatment. Its intensive use is linked with skeletal adverse effects such as reduced bone formation and bone loss, and yet little information is available on molecular mechanisms underlying MTX-induced impaired bone formation. This study investigated the effects of MTX treatment at a c...
Article
Full-text available
Methotrexate (MTX) treatment for childhood malignancies has shown decreased osteogenesis and increased adipogenesis in bone marrow stromal cells (BMSCs), leading to bone loss and bone marrow adiposity, for which the molecular mechanisms are not fully understood. Currently, microRNAs (miRNAs) are emerging as vital mediators involved in bone/bone mar...
Article
Full-text available
Intensive methotrexate (MTX) treatment for childhood malignancies decreases osteogenesis but increases adipogenesis from the bone marrow stromal cells (BMSCs), resulting in bone loss and bone marrow adiposity. However, the underlying mechanisms are unclear. While microRNAs (miRNAs) have emerged as bone homeostasis regulators and miR-542-3p was rece...
Article
Previous studies have shown that administration of antimetabolite methotrexate (MTX) caused a reduced trabecular bone volume and increased marrow adiposity (bone/fat switch), for which the underlying molecular mechanisms and recovery potential are unclear. Altered expression of microRNAs (miRNAs) has been shown to be associated with dysregulation o...
Article
Growth plate cartilage injuries often result in bony repair at the injury site and premature mineralization at the uninjured region causing bone growth defects, for which underlying mechanisms are unclear. With the prior microarray study showing upregulated bone morphogenetic protein (BMP) signalling during the injury site bony repair and with the...
Article
Intensive use of methotrexate (MTX) and/or dexamethasone (DEX) for treating childhood malignancies is known to cause chondrocyte apoptosis and growth plate dysfunction leading to bone growth impairments. However, mechanisms remain vague and it is unclear whether MTX and DEX combination treatment could have additive effects in the growth plate defec...
Article
Cancer chemotherapy can significantly impair the bone formation and cause myelosuppression; however, their recovery potentials and mechanisms remain unclear. This study investigated the roles of the β‐catenin signaling pathway in bone and bone marrow recovery potentials in rats treated with antimetabolite methotrexate (MTX) (five once‐daily injecti...
Article
It has been well-established that malondialdehyde (MDA), which is generated during the process of lipid peroxidation, is a commonly known biomarker for oxidative stress. Therefore, the serum levels of MDA are detected by using the lipid peroxidation assay with commercially available kit to determine the induction of oxidative stress in rat models.
Article
Despite more attention to cell migration from circulation into the bone marrow (BM), particularly homing of haematopoietic stem/progenitor cells, the process and mechanisms of cell mobilisation from the BM into the circulation remain largely underexplored. The process of cell mobilisation or transcellular cell migration from BM into the circulation...
Article
Methotrexate (MTX), a widely used antimetabolite in paediatric cancer to treatment, has been widely reported to cause bone loss and bone marrow (BM) microvascular (particularly sinusoids) damage. Investigations must now investigate how MTX‐induced bone loss and microvasculature damage can be attenuated/prevented. In the present study, we examined t...
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Opioids are widely administered to alleviate pain, including chronic pain in advanced cancer patients. Among opioids, morphine is one of the most clinically effective drugs for the palliative management of severe pain. In the last few decades, there has been a debate around the possible influence of opioids such as morphine on tumour growth and met...
Article
Critical limb ischemia (CLI) is the advanced stage of peripheral artery disease spectrum and is defined by limb pain or impending limb loss because of compromised blood flow to the affected extremity. Current conventional therapies for CLI include amputation, bypass surgery, endovascular therapy, and pharmacological approaches. Although these conve...
Article
Wound healing is a complex but a fine‐tuned biological process in which human skin has the ability to regenerate itself following damage. However, in particular conditions such as deep burn or diabetes the process of wound healing is compromised. Despite investigations on the potency of a wide variety of stem cells for wound healing, adipose‐derive...
Article
Dexamethasone (Dex) is known to cause significant bone growth impairment in childhood. Although previous studies have suggested roles of osteocyte apoptosis in the enhanced osteoclastic recruitment and local bone loss, whether it is so in the growing bone following Dex treatment requires to be established. The current study addressed the potential...
Article
Cancer chemotherapy can cause significant damage to the bone marrow (BM) microvascular (sinusoidal) system. Investigations must now address whether and how BM sinusoidal endothelial cells (SECs) can be protected during chemotherapy. Herein we examined the potential protective effects of genistein, a soy‐derived flavonoid, against BM sinusoidal dama...
Article
Chemotherapeutic agents are very well evident extrinsic stimuli for causing damage to endothelial cells. Methotrexate is an antimetabolite commonly used to treat solid tumours and paediatric cancers. However, studies on the effect(s) of methotrexate on bone marrow microvascular system are inadequate. In the current study, we observed a significant...
Article
Cancer treatments with cytotoxic drugs have been shown to cause bone loss. However, effects on bone are less clear for ErbB‐targeting tyrosine kinase inhibitors or their combination use with cytotoxic drugs. This study examined the effects of individual or combination treatments with breast cancer drugs lapatinib (a dual ErbB1/ErbB2 inhibitor) and...
Article
Faulty bony repair causes dysrepair of injured growth plate cartilage and bone growth defects in children; however, the underlying mechanisms are unclear. Recently, we observed the prominent induction of neurotrophin‑3 (NT-3) and its important roles as an osteogenic and angiogenic factor promoting the bony repair. The current study investigated its...
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Although bone marrow and bone toxicities have been reported in breast cancer survivors, preventative strategies are yet to be developed. Clinical studies suggest consumption of long chain omega-3 polyunsaturated fatty acids (LCn3PUFA) can attenuate age-related bone loss, and recent animal studies also revealed benefits of LCn3PUFA in alleviating bo...
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It is very well known that bone marrow (BM) microvasculature may possess a crucial role in the maintenance of homeostasis of BM due to mutual interactions between BM microvascular system and other physiological functions including haematopoiesis and osteogenesis. Chemotherapy and radiotherapy are known as main approaches for cancer treatment and al...
Article
Intensive cancer chemotherapy causes significant bone loss, for which the mechanisms remain unclear and effective treatments are lacking. This is a significant issue particularly for childhood cancers, as the most common ones have a >75% cure rate following chemotherapy; there is an increasing population of survivors who live with chronic bone defe...
Article
Neurotrophins and their receptors are key molecules that are known to be critical in regulating nervous system development and maintenance and have been recognized to be also involved in regulating tissue formation and healing in skeletal tissues. Studies have shown that neurotrophins and their receptors are widely expressed in skeletal tissues, im...
Article
Full-text available
Intensive cancer chemotherapy is known to cause bone defects, which currently lack treatments. This study investigated the effects of polyphenol resveratrol (RES) in preventing bone defects in rats caused by methotrexate (MTX), a commonly used antimetabolite in childhood oncology. Young rats received five daily MTX injections at 0.75 mg/kg/day. RES...
Article
Full-text available
Injured growth plate is often repaired by bony tissue causing bone growth defects, for which the mechanisms remain unclear. Because neurotrophins have been implicated in bone fracture repair, here we investigated their potential roles in growth plate bony repair in rats. After a drill-hole injury was made in the tibial growth plate and bone, increa...
Article
Angiogenesis plays a pivotal role in bone formation, remodeling, and fracture healing. The regulation of angiogenesis in the bone microenvironment is highly complex and orchestrated by intercellular communication between bone cells and endothelial cells. Here, we report that EGF-like domain 7 (EGFL7), a member of the epidermal growth factor (EGF) r...
Article
Methotrexate (MTX) chemotherapy is known to cause bone loss which lacks specific preventative treatments, although clinically folinic acid is often used to reduce MTX toxicity in soft tissues. This study investigated damaging effects of MTX injections (0.75 mg/kg/day for 5 days) in rats and potential protective benefits of fish oil (0.25, 0.5, or 0...
Article
Full-text available
Cancer chemotherapy has been shown to induce long-term skeletal side effects such as osteoporosis and fractures; however, there are no preventative treatments. This study investigated the damaging effects of anti-metabolite methotrexate (MTX) subcutaneous injections (0.75 mg/kg BW) for five days and the potential protective benefits of daily oral g...
Article
Full-text available
Cancer chemotherapy can cause osteopenia or osteoporosis, and yet the underlying mechanisms remain unclear, and currently, no preventative treatments are available. This study investigated damaging effects of 5-fluorouracil (5-FU) on histological, cellular, and molecular changes in the tibial metaphysis and potential protective benefits of emu oil...

Citations

... Previous cellular and pathological findings revealed damaging effects on bone and bone marrow vasculature following MTX chemotherapy in rats, particularly at day nine after the first MTX injection (a time point known to have the most significant histological damage) [17,33]. Very recently, we found that elevated expression of Notch2 mRNA (by RT-PCR) and Notch2 protein (by Western blotting) in bone is associated with bone damage in rats, and that supplementary treatment with Notch2-specific antibody against the negative regulatory region of Notch2 receptor (NRR2) protected trabecular bone from MTX-induced damage [50]. In the current study, as a first step to determine whether MTX treatment alters NICD2 protein expression in endothelial cells in bone, immunohistochemical staining was conducted using tibia sections collected from different time points after MTX treatment. ...
... To investigate the possible role of anti-Notch2 (NRR2) antibody in protecting endothelial cells against MTX damage, cells (at reaching 70% confluency) were treated with saline or MTX (10 µM) along with either the anti-ragweed antibody as control IgG (10 µg mL −1 ) or the anti-Notch2 antibody (10 µg mL −1 ) for 24 h, after which time the cells were harvested and conditioned medium was collected. The selected dose for MTX treatment in vitro is the chemotherapy relevant dose for MTX in cell culture studies [17,43,44]. The dose chosen for anti-Notch2 antibody treatment has previously been used in different in vitro studies to block Notch2 receptor activity effectively [36,44,45]. ...
... There are two types of Vit D; the main form 25-hydroxycholecalciferol (25 (OH) D) and hormonal form 1, 25-dihydroxycholecalciferol (1, 25 (OH)2D) in the liver and kidneys (Young et al. 2021). Several diseases have been found in animal studies to respond positively to Vit D and 1, 25 (OH)2D or their analogs, there have also been promising observations regarding adequate Vit D nutrition and cancer prevention that affects the development of cancer (Liu et al. 2021). O'Brien et al.(2022) stated that statins are routinely used to treat hyperlipidemia, but may also have antineoplastic effects. ...
... Previously, the regulation of the miRNA-6315 network was found to be potentially involved in hyperplasia of mammary glands and cell proliferation during liver regeneration [22,23]. Our recent study has shown that miR-6315 was upregulated in bones of MTX-treated rats, which might be associated with bone/bone marrow fat imbalance by directly targeting Smad2 [24]. However, the underlying mechanisms by which miR-6315 regulates osteogenic and adipogenic differentiation remain unknown. ...
... A previous report indicated that miR-204 inhibits the osteogenesis and promotes adipogenesis of mesenchymal stem cells by targeting Runx2 [48]. In the regulatory aspect of osteogenesis and chondrogenesis, RUNX2 has been regarded as a pivotal transcription factor [49]. Circ_2929 and circ_ARHGAP35-miR-204-5p-Runx2 may be potential axial regulators of osteoblast differentiation ( Figure 2C). ...
... Dex is a synthetic GC that has been widely used to treat inflammatory and autoimmune diseases. However, clinical evidence shows that the prolonged treatment with Dex causes growth retardation in treated children by triggering chondrocyte apoptosis within the growth plate [19,20]. In this study, we found that KLF2 expression was increased in chondrocytes of the tibial growth plate in Dex-treated rats. ...
... А В С who had found that chemotherapy with methotrexate inhibited bone formation by inhibiting the activation of Wnt/β-catenin signaling pathway. As a result, the differentiation of osteoblastic cells providing mineralization of the bone matrix [13,14,15] was inhibited. King (2012) also found that methotrexate treatment promoted the formation of osteoclasts in the long bones of rats by increasing the level of proinflammatory cytokines and enhancing the activation of NF-kβ transcription factor. ...
... Oxidative stress was assessed by using an assay kit (MAK085, Sigma-Aldrich, St. Louis, MO, USA), which determines the plasma level of malondialdehyde (MDA), an end product of lipid peroxidation, via the reaction of MDA with thiobarbituric acid (TBA) to form a colorimetric product in proportion with the MDA present [30]. In this assessment, 20 µL of plasma was gently mixed with 500 µL of 42 nM sulfuric acid in a microcentrifuge tube. ...
... In contrast, ~40% of ILC2P were assigned to the sinusoidal niche. These data indicate that ILC progenitor populations are heterogeneous in their localization within the BM, and the majority of the multipotential ILCPs are present in the sinusoid niche, which is considered not only a major site of hematopoiesis but also the gate for cell trafficking in and out of the BM (32). To determine whether these BM ILC progenitors emigrate to the peripheral blood, we took a BM CellTracker microinjection approach (33). ...
... demonstrated that oral ica treatment prevents bone loss in iron-overloaded mice and inhibited the differentiation and function of osteoclasts. in addition, ica reduces bone loss induced by methotrexate chemotherapy in rats (23). as these studies demonstrate the osteoporosis-related activity of ica, it was hypothesized that ica may exert a protective effect on Taa-induced bone loss. ...