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Circulating sRANKL, Periostin, and Osteopontin as Biomarkers for the Assessment of Activated Osteoclastogenesis in Myeloma Related Bone Disease.

The hallmark of multiple myeloma is myeloma related bone disease. Interactions between myeloma plasma cells (MPCs), stromal cells, and the bone marrow (BM) microenvironment play a critical role in the pathogenesis of MBD. Bone remodeling is severely dysregulated with the prevalence of osteoclast activity. We aimed to assess circulating levels of sRANKL, periostin, and osteopontin as osteoclast activators in NDMM patients at diagnosis and in the course of treatment, correlations with clinical and laboratory data, and to evaluate their potential as additional biomarkers for the assessment of MBD

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… Another protein associated with bone metabolism is the extracellular matrix (ECM) protein periostin, which is produced primarily by stromal mesenchymal cells and is mainly expressed in the periosteum [ 20 , 21 ]. …

Oral care and the use of bone-targeted agents in patients with metastatic cancers: A practical guide for dental surgeons and oncologists.

BackgroundBone-targeted agents such as bisphosphonates and the RANKL antibody have revolutionised the care of patients with bone metastases. There has, however been increasing concern about the oral health of these patients and in particular osteonecrosis of the jaw (ONJ), especially with the increasing use of these agents at higher potencies for greater periods of time.MethodsA review of the published data in PubMed and meeting abstracts was performed to examine incidence, risk factors, pathogenesis, clinical course and management of osteonecrosis of the jaw with focus on cancer patients trea

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… Nevertheless, stopping the bisphosphonate would remove any acute influences on the periosteum and soft tissues, and could potentially improve the healing process. [5] , [31] . …

RANK, RANKL and osteoprotegerin in bone biology and disease.

Upon the discovery of RANK, RANKL and OPG in the late 1990s, their importance in the maintenance of the skeletal structure and their dramatic role in bone disease were largely unexpected. In recent years the understanding of these proteins, in particular their regulation, has greatly increased. This review aims to bring the interested reader up to date with the latest news and views on the mechanisms controlling bone resorption in normal and pathological conditions.

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… These authors found that OPG inhibited both the release of osteoclasts from the periosteum and adherence of the osteoclasts to the bone surface, therefore inhibiting bone resorption [ 29 ]. …

Potential Targeting Mechanisms for Bone-Directed Therapies.

Bone development is characterized by complex regulation mechanisms, including signal transduction and transcription factor-related pathways, glycobiological processes, cellular interactions, transportation mechanisms, and, importantly, chemical formation resulting from hydroxyapatite. Any abnormal regulation in the bone development processes causes skeletal system-related problems. To some extent, the avascularity of cartilage and bone makes drug delivery more challenging than that of soft tissues. Recent studies have implemented many novel bone-targeting approaches to overcome drawbacks. Howe

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… Expression and lineage analysis of chondrocytes showed selective expression of DDR-2 at the initial stages of bone formation in the resting zone and proliferating chondrocytes as well as periosteum. … Newborn mice showed tetranectin immune reaction in the newly formed woven bone around the cartilage and along the periosteum, while no activity was observed in the growth plate or surrounding skeletal muscle. …

The inhibition of RANKL-induced osteoclastogenesis through the suppression of p38 signaling pathway by naringenin and attenuation of titanium-particle-induced osteolysis.

The aim of this study was to assess the effect of naringenin on osteoclastogenesis and titanium particle-induced osteolysis. Osteolysis from wear-induced particles and aseptic loosening are the most frequent late complications of total joint arthroplasty leading to revision of the prosthesis. Osteolysis during aseptic loosening is most likely due to increased bone resorption by osteoclasts. Through in vitro studies, we demonstrated that naringenin, a naturally occurring flavanone in grapefruit and tomatoes, exerts potent inhibitory effects on the ligand of the receptor activator of nuclear fac

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… group): sham phosphate buffered saline (PBS) control (sham), Ti particle osteolysis with PBS vehicle (vehicle), and Ti particle osteolysis with low NAR (10 mg/kg/day; low) and Ti particle osteolysis with high NAR (25 mg/kg/day; high). 2 days after the implantation, NAR or PBS was injected into the periosteum …

Macrophage miR-149-5p induction is a key driver and therapeutic target for BRONJ.

Bisphosphonate-related (BP-related) osteonecrosis of the jaw (BRONJ) is one of the severe side effects of administration of BPs, such as zoledronic acid (ZA), which can disrupt the patient's quality of life. Although the direct target of skeletal vasculature and bone resorption activity by BPs has been phenomenally observed, the underlying mechanism in BRONJ remains largely elusive. Thus, it is urgently necessary to discover effective therapeutic targets based on the multifaceted underlying mechanisms in the development of BRONJ. Here, we determined the inhibitory role of ZA-treated macrophage

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… 30624969 27 Stefanowski J et al Spatial distribution of macrophages during callus formation and maturation reveals close crosstalk between macrophages and newly forming vessels Front Immunol 2019 10 2588 10.3389/fimmu.2019.02588 31956322 PMC6953593 28 Gao B et al Macrophage-lineage TRAP+ cells recruit periosteum-derived …

Targeting the BMP Pathway in Prostate Cancer Induced Bone Disease.

From the 33,000 men in the U.S. who die from prostate cancer each year, the majority of these patients exhibit metastatic disease with bone being the most common site of metastasis. Prostate cancer bone metastases are commonly blastic, exhibiting new growth of unhealthy sclerotic bone, which can cause painful skeletal related events. Patient's current care entails androgen deprivation therapy, anti-resorptive agents, radiation, and chemotherapy to help control the spread of the cancer but little intervention is available to treat blastic bone disease. The transforming growth factor beta (TGFβ)

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… Representative histology confirmed the lytic nature of PC3 cells that can be seen destroying trabecular bone as well as cortical bone which led to growth outside the periosteum ( Figure 3G ). …

Spinal metastasis: narrative reviews of the current evidence and treatment modalities.

The treatment for spinal metastasis has evolved significantly during the past decade. An advancement in systemic therapy has led to a prolonged overall survival in cancer patients, thus increasing the incidence of spinal metastasis. In addition, with the improved treatment armamentarium, the prediction of patient survival using traditional prognostic models may have limitations and these require the incorporation of some novel parameters to improve their prognostic accuracy. The development of minimally-invasive spinal procedures and minimal access surgical techniques have facilitated a quicke

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… Up to 95% of patients experience pain as their initial symptom. 16 , 17 Pain in spinal metastases can be caused by tumour invasion and expansion in the vertebral body causing pressure on the periosteum, spinal instability due to vertebral destruction, fractures or neural compression. …

KIAA1429-mediated M6A methylation inhibits osteoclast differentiation via stabilizing Lrp4 mRNA and protects against osteoporosis.

N6-methyladenosine (m6A) is a novel epigenetic modification that has been reported to be involved in the progression of osteoporosis (OP), providing new insights into the pathogenesis of OP. The methyltransferases KIAA1429 [also known as virus-like m6A methyltransferase-associated protein (VIRMA)] participates in various essential biological processes by regulating target gene expression levels. However, the function of KIAA1429-mediated m6A modification in OP progression remains unclear. This study aimed to investigate the biological roles and potential underlying mechanisms of KIAA1429 in OP

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… An internal pressure syringe was inserted through the defect, and 10 μL of Kiaa1429 AAV (1 × 10 11 vg/mL) was injected directly into the bone marrow cavity of the femur by penetrating the periosteum and bone cortex. … overexpression inhibited bone resorption in OVX mice To determine whether KIAA1429 directly regulates m 6 A-mediated methylation during bone resorption, we constructed an adeno-associated virus (AAV) delivery system to overexpress Kiaa1429 by injection into the femoral bone marrow cavity through the periosteum …

Primary Osteoporosis Induced by Androgen and Estrogen Deficiency: The Molecular and Cellular Perspective on Pathophysiological Mechanisms and Treatments.

Primary osteoporosis is closely linked to hormone deficiency, which disrupts the balance of bone remodeling. It affects postmenopausal women but also significantly impacts older men. Estrogen can promote the production of osteoprotegerin, a decoy receptor for RANKL, thereby preventing RANKL from activating osteoclasts. Furthermore, estrogen promotes osteoblast survival and function via activation of the Wnt signaling pathway. Likewise, androgens play a critical role in bone metabolism, primarily through their conversion to estrogen in men. Estrogen deficiency accelerates bone resorption throug

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… It is nourished by Haversian and Volkmann’s canals as well as canaliculi [ 28 , 29 ], and is enveloped by connective tissues known as the periosteum and endosteum. Cortical bone has a lower surface-to-volume ratio compared to trabecular bone. … Osteoprogenitor Cells (OPCs) Bone repair and regeneration are initiated by osteoprogenitor (osteogenic) cells found in various locations, such as the epiphysis, marrow [ 38 ], growth plate, cranial suture [ 39 ], bone canals, periosteum, and endosteum [ 40 ]. …

Treatment of Cancer Pain by Targeting Cytokines.

Inflammation is one of the most important causes of the majority of cancer symptoms, including pain, fatigue, cachexia, and anorexia. Cancer pain affects 17 million people worldwide and can be caused by different mediators which act in primary efferent neurons directly or indirectly. Cytokines can be aberrantly produced by cancer and immune system cells and are of particular relevance in pain. Currently, there are very few strategies to control the release of cytokines that seems to be related to cancer pain. Nevertheless, in some cases, targeted drugs are available and in use for other diseas

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… The acidic microenvironment adjacent to the richly innervated periosteum is a mechanism associated with pain in metastatic bone cancer [ 25 ]. Tumor-induced release of protons and acidosis might be particularly important in the generation of bone cancer pain [ 26 ]. …

Mechanisms inducing low bone density in Duchenne muscular dystrophy in mice and humans.

Patients affected by Duchenne muscular dystrophy (DMD) and dystrophic MDX mice were investigated in this study for their bone phenotype and systemic regulators of bone turnover. Micro-computed tomographic (µCT) and histomorphometric analyses showed reduced bone mass and higher osteoclast and bone resorption parameters in MDX mice compared with wild-type mice, whereas osteoblast parameters and mineral apposition rate were lower. In a panel of circulating pro-osteoclastogenic cytokines evaluated in the MDX sera, interleukin 6 (IL-6) was increased compared with wild-type mice. Likewise, DMD patie

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… Comparison of osteogenic ability of rat mesenchymal stem cells from bone marrow, periosteum, and adipose tissue. Calcif Tissue Int. 2008;82:238–247. doi: 10.1007/s00223-008-9112-y. 53. Hu JC, Yamakoshi Y. Enamelin and autosomal-dominant amelogenesis imperfecta. …

[Precise application of Traditional Chinese Medicine in minimally-invasive techniques].

The miminally-invasive techniques of traditional Chinese medicine(TCM) uses different types of acupuncture needles to treat diseased locatio … clude: meridian acupoint stimulation; cutaneous stimulation; fascia stimulation; mucle stimulation; periosteum stimulation. The clinical application of these techniques has enriched the drug-free therapies of traditional Chinese medicine and achieved excellent outcomes, but at the same time it also raises an important question. How can we apply these minimal …

The BE (2)-M17 neuroblastoma cell line: revealing its potential as a cellular model for Parkinson's disease.

Parkinson's disease is a pathology with a wide range of in vivo and in vitro models available. Among these, the SH-SY5Y neuroblastoma cell line is one of the most employed. This model expresses catecholaminergic markers and can differentiate and acquire various neuronal phenotypes. However, challenges persist, primarily concerning the variability of growth media, expression of dopaminergic markers, and a wide variety of differentiation protocols have been reported in the literature without direct comparison between them. This lack of standardized differentiation conditions impacts result repro

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… Effects of DMEM and RPMI 1640 on the biological behavior of dog periosteum-derived cells. Cytotechnology 59 103–111. 10.1007/s10616-009-9200-5 Xicoy H., Wieringa B., Martens G. J. M. (2017). The SH-SY5Y cell line in Parkinson’s disease research: A systematic review. Mol. …

Regulatory role of PI3K/Akt/WNK1 signal pathway in mouse model of bone cancer pain.

In the advanced stage of cancer, the pain caused by bone metastasis is unbearable, but the mechanism of bone cancer pain (BCP) is very complicated and remains unclear. In this study, we used 4T1 mouse breast cancer cells to establish a bone cancer pain model to study the mechanism of BCP. Then the paw withdrawal mechanical threshold (PWMT) and the hematoxylin-eosin staining were used to reflect the erosion of cancer cells on tibia tissue. We also determined the role of proinflammatory factors (TNF-α, IL-17, etc.) in BCP by the enzyme-linked immunosorbent assay in mouse serum. When GSK690693, a

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… Therefore, Schwei et al. injected NCTC2472 osteosarcoma cells into the femur to destroy periosteum, established a metastatic bone tumor model and studied the chemical changes of spinal cord and related dorsal root ganglia, which promoted the study of the mechanism of bone cancer pain. …

Amyloidoses in Onco-Nephrology Practice: A Multidisciplinary Case-Based Conference Report.

Introduction and objectiveAmyloidoses are a heterogeneous group of disorders resulting from deposition of amyloid fibrils into extracellular tissues. While the kidneys are one of the most frequent sites of amyloid deposition, amyloid deposits can also affect a wide range of organ systems, including the heart, liver, gastrointestinal tract, and peripheral nerves. The prognosis of amyloidosis, especially with cardiac involvement, remains poor; however, a collaborative approach applying new tools for diagnosis and management may improve outcomes. In September 2021, the Canadian Onco-Nephrology In

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… Periosteum was positive for Congo red staining. Echocardiogram showed LV hypertrophy with left atrial enlargement. …

Management of Long Bones Metastatic Disease: Concepts That We All Know but Not Always Remember.

Bones are the third most common site of metastatic disease. Treatment is rarely curative; rather, it seeks to control disease progression and palliate symptoms. Imaging evaluation of a patient with symptoms of metastatic bone disease should begin with plain X-rays. Further imaging consists of a combination of (PET)-CT scan and bone scintigraphy. We recommend performing a biopsy after imaging workup has been conducted. Metastatic bone disease is managed with a combination of systemic treatment, radiotherapy (RT), and surgery. External beam RT (EBRT) is used for pain control and postoperatively

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… Innervation of the periosteum explains why bone pain shares similar qualities with neurogenic pain: progressive, poorly localized, of deep boring quality, and accompanied by episodes of aches, burns and stabbing discomfort. 14 , 15 This pain is also described as being worse at night and is not relieved …

Infectious Diseases

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… Imaging of choice for specific body sites (vertebrae, diabetic foot) (sens 72%) ULTRASOUND —fluid collection adjacent to the bone without intervening soft tissue, elevation of the periosteum by >2 mm, and thickening of the periosteum. …

Exploring the Efficacy of Combining Radiofrequency Thermal Ablation or Microwave Ablation with Vertebroplasty for Pain Control and Disease Management in Metastatic Bone Disease-A Systematic Review.

BACKGROUND: Interventional radiology techniques have become pivotal in recent years in managing metastatic bone disease, which frequently results in skeletal complications such as fractures and severe pain. Thermoablative methods like radiofrequency ablation (RFA) and microwave ablation (MWA), when combined with vertebroplasty (VP), are proving increasingly beneficial for these patients. METHODS: The search was independently conducted by two radiologists on MEDLINE databases, using specified strings up to April 2024. Methodological quality was assessed using PRISMA guidelines. Studies meeting

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… Similar to thermal ablation techniques, MWA induces coagulation necrosis within the targeted tissue, leading to reduced production of nerve-stimulating cytokines and the destruction of pain nerve fibers in the periosteum and bone cortex. …

Neurophysiological Mechanisms Related to Pain Management in Bone Tumors.

BackgroundPrimary and metastatic bone tumor incidence has increased in the previous years. Pain is a common symptom and is one of the most important related factors to the decrease of quality of life in patients with bone tumor. Different pain management strategies are not completely effective and many patients afflicted by cancer pain cannot be controlled properly. In this sense, we need to elucidate the neurophysiology of cancer-induced pain, contemplating other components such as inflammation, neuropathies and cognitive components regarding bone tumors, and thus pave the way for novel thera

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… In this sense, cancer-associated bone pain is a consequence of a large number of sensory and sympathetic innervations of the bone periosteum, bone marrow and bone matrix. …