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Can Traditional Straight-leg Swaddling Influence Developmental Dysplasia of the Femoral Trochlea? An In Vivo Study in Rats.

BACKGROUND: It has been reported that trochlear dysplasia occurs very early in development, and environmental factors like swaddling may cau … ransduction-associated proteins (such as, TRPV4/ Piezo1 and CollagenⅡ) in cartilage and subchondral osteocytes. It will also be helpful to further investigate the mechanism of developmental femoral trochlea dysplasia caused by biomechanical changes.

The skeleton in primary hyperparathyroidism: a review focusing on bone remodeling, structure, mass, and fracture.

The mechanisms behind the influence of PHPT on the skeleton are closely connected with bone turnover. Throughout life, the skeleton is conti … , the "acute" regulatory actions of PTH on serum calcium are probably accompliced via activation of osteocytes and lining cells. A second mechanism of PTH in bone is the regulation of bone remodeling. The action seems to be an increased recruitment from osteoblastic precursor cells and activation of mature osteoclasts. It is supposed that these responses are …

Rare diseases: a challenge in paediatric dentistry.

Rare diseases are an often an overlooked public health problem. Although they are infrequent, occurring on average in 100-500 people per mil … roduction of 1,25 -dihydroxy-vitamin D (1,25(OH)2D). PHEX protein is also expressed in osteoblasts, osteocytes, and odontoblasts. Regardless of FGF23's systemic effects on phosphate homeostasis, odontoblast differentiation, and dentin formation, its overexpression directly reduces osteoblast differentiation and matrix mineralisation. In patients with XLH, th …

Pathological Crosstalk between Metastatic Breast Cancer Cells and the Bone Microenvironment.

Bone is the most common metastatic site in breast cancer. Upon arrival to the bone, disseminated tumor cells can undergo a period of dormancy but often eventually grow and hijack the bone microenvironment. The bone marrow microenvironment consists of multiple cell types including the bone cells, adipocytes, endothelial cells, and nerve cells that all have crucial functions in the maintenance of bone homeostasis. Tumor cells severely disturb the tightly controlled cellular and molecular interactions in the bone marrow fueling their own survival and growth. While the role of bone resorbing osteo

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… This suggests a protective role of Cx43 in osteocytes against breast cancer growth in vivo. … Given that osteocytes are a major source of RANKL it is likely that treatment effects could be partially mediated by osteocytes. Propranolol, a β-AR antagonist, is commonly used in the treatment of hypertension. …

New agents in the Treatment of Myeloma Bone Disease.

Patients with multiple myeloma develop a devastating bone disease driven by the uncoupling of bone remodelling, excess osteoclastic bone resorption and diminished osteoblastic bone formation. The bone phenotype is typified by focal osteolytic lesions leading to pathological fractures, hypercalcaemia and other catastrophic bone events such as spinal cord compression. This causes bone pain, impaired functional status, decreased quality of life and increased mortality. Early in the disease, malignant plasma cells occupy a niche environment that encompasses their interaction with other key cellula

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… Osteocytes Regulate Bone Remodelling in MBD Osteocytes are the most abundant bone cells, making up 95% of all bone cells [ 44 ]. … Furthermore, osteocytes are able to create a network of interactions from cell-to-cell contact between each other to cells on the cell surface and are able to distribute cytokines throughout the bone marrow, thus making osteocytes the central regulators of bone homeostasis and highlighting how osteocytes …

Targeting strategies for bone diseases: signaling pathways and clinical studies.

Since the proposal of Paul Ehrlich's magic bullet concept over 100 years ago, tremendous advances have occurred in targeted therapy. From the initial selective antibody, antitoxin to targeted drug delivery that emerged in the past decades, more precise therapeutic efficacy is realized in specific pathological sites of clinical diseases. As a highly pyknotic mineralized tissue with lessened blood flow, bone is characterized by a complex remodeling and homeostatic regulation mechanism, which makes drug therapy for skeletal diseases more challenging than other tissues. Bone-targeted therapy has b

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… in vivo or in vitro. 71 Apart from direct RANKL secretion by osteocyte apoptosis, evidence has also indicated that apoptotic osteocytes trigger RANKL production in healthy osteocytes nearby by activating the P2X7 and pannexin-1 receptors under ATP stimuli. 72 Recent studies also suggested that damage-associated … osteoblasts, and eventually differentiate into bone lining cells and osteocytes. …

Myeloma bone disease: pathogenesis and management in the era of new anti-myeloma agents.

IntroductionMultiple myeloma (MM) is a malignancy of plasma cells with characteristic bone disease. Despite recent great strides achieved in MM treatment owing to the implementation of new anti-MM agents, MM is still incurable and bone destruction remains a serious unmet issue in patients with MM.ApproachIn this review, we will summarize and discuss the mechanisms of the formation of bone disease in MM and the available preclinical and clinical evidence on the treatment for MM bone disease.ConclusionsMM cells produce a variety of cytokines to stimulate receptor activator of nuclear factor-κB l

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… RANKL and sclerostin are over-produced by osteocytes. … Therefore, TAK1 activation is vital for MM cell growth and survival and bone destruction Osteocytes Osteocytes are the most abundant cells in bone. Osteocytes are derived from osteoblasts and embedded in bone. …

Early-Onset Osteoporosis: Rare Monogenic Forms Elucidate the Complexity of Disease Pathogenesis Beyond Type I Collagen.

Early-onset osteoporosis (EOOP), characterized by low bone mineral density (BMD) and fractures, affects children, premenopausal women and men aged <50 years. EOOP may be secondary to a chronic illness, long-term medication, nutritional deficiencies, etc. If no such cause is identified, EOOP is regarded primary and may then be related to rare variants in genes playing a pivotal role in bone homeostasis. If the cause remains unknown, EOOP is considered idiopathic. The scope of this review is to guide through clinical and genetic diagnostics of EOOP, summarize the present knowledge on rare monoge

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… located in the dendrites of the osteocytes, supporting a role in mechanotransduction. ( 118 ) Therefore, PLS3 could be especially important for osteocyte function (Fig. 4 C ). … The fingerprint of dead osteocytes are highly mineralized lacunae. …

The link between bone-derived factors osteocalcin, fibroblast growth factor 23, sclerostin, lipocalin 2 and tumor bone metastasis.

The skeleton is the third most common site of metastatic disease, which causes serious bone complications and short-term prognosis in cancer patients. Prostate and breast cancers are responsible for the majority of bone metastasis, resulting in osteolytic or osteoblastic lesions. The crosstalk between bone cells and their interactions with tumor cells are important in the development of lesions. Recently, both preclinical and clinical studies documented the clinical relevance of bone-derived factors, including osteocalcin (OC) and its undercarboxylated form (ucOC), fibroblast growth factor 23

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… Osteoblasts, osteocytes, and osteoclasts express the FGFR/αKlotho coreceptor. The specific knockout of αKlotho in osteocytes can lead to the osteogenic enhancement and increased bone mass ( 72 ). … According to Vlot et al. ( 48 ), the serum level of FGF23 was unchanged in prostate cancer ( 48 ), although prostate cancer cells can stimulate FGF23 expression in osteocytes ( 49 ). …

Immune reprogramming in the bone marrow microenvironment: a new perspective on the bone immune microenvironment of postmenopausal osteoporosis.

Research on postmenopausal osteoporosis (PMOP), a common bone metabolic disease, has traditionally focused on bone loss and imbalance in bone remodeling. However, with the development of bone immunology, the complex interactions between immune cells and bone cells in the bone marrow microenvironment have gradually been revealed, and "immune reprogramming" is considered a key factor driving the persistent bone loss in PMOP. Current evidence indicates that the postmenopausal bone marrow microenvironment undergoes significant structural and functional changes. These changes are characterized by a

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… Osteocytes can sense mechanical stress and metabolic changes, communicating with neighboring osteocytes, osteoblasts, and osteoclast precursors on the bone surface through gap junctions and EVs ( 60 ). … In a healthy bone environment, osteocytes, osteoblasts, and osteoclasts form a dynamically balanced “osteocyte–bone remodeling coupling unit.” …

Исцеление литических повреждений и восстановление костного здоровья в множестве миеломы посредством ингибиции склеростинов.

Множественная миелома (ММ) связана с изнурительным заболеванием костей, которое создает серьезные терапевтические проблемы. Болезнь костей MM характеризуется повышенной ресорбцией костей и подавлением остеобластов, что препятствует ремонту поврежденных костей. Склеростин, антагонист Wnt сигнализатора, выше у пациентов MM, и его ингибиция с нейтрализующим антителом (Scl-ab) была продемонстрирована для восстановления остеобластной функции в мышиных моделях MM. Однако остается неясным, может ли Scl-ab способствовать ремонту скелета, обеспечивать эффективный контроль над опухолью в сочетании с ант

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… White arrows denote sclerostin + osteocytes. … White arrows denote sclerostin + osteocytes. …

Immune mediated support of metastasis: Implication for bone invasion.

Bone is a common organ affected by metastasis in various advanced cancers, including lung, breast, prostate, colorectal, and melanoma. Once a patient is diagnosed with bone metastasis, the patient's quality of life and overall survival are significantly reduced owing to a wide range of morbidities and the increasing difficulty of treatment. Many studies have shown that bone metastasis is closely related to bone microenvironment, especially bone immune microenvironment. However, the effects of various immune cells in the bone microenvironment on bone metastasis remain unclear. Here, we describe

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… Osteocytes and bone metastasis Osteocytes are the most abundant cells in bone and develop from osteoblasts. As osteocytes mature, they form a strong network of dendrites that touch each other and can interact with other cells [ 232 ]. … However, some studies have shown that osteocytes can inhibit bone metastasis. …

The Bone Extracellular Matrix as an Ideal Milieu for Cancer Cell Metastases.

Bone is a preferential site for cancer metastases, including multiple myeloma, prostate, and breast cancers.The composition of bone, especially the extracellular matrix (ECM), make it an attractive site for cancer cell colonization and survival. The bone ECM is composed of living cells embedded within a matrix composed of both organic and inorganic components. Among the organic components, type I collagen provides the tensile strength of bone. Inorganic components, including hydroxyapatite crystals, are an integral component of bone and provide bone with its rigidity. Under normal circumstance

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… These non-dividing and trapped osteoblasts are called osteocytes [ 10 ]. Osteocytes are terminally differentiated osteoblasts that reside in a small cavity called a lacunae ( Figure 2 ) [ 10 ]. Osteocytes make up about 90–95% of all bone cells [ 22 ]. … Osteocytes also regulate osteoclast activation during bone remodeling [ 28 ]. It has been proposed that osteocytes secrete osteoclast-inhibitors, such as osteoprotegerin, and only when a population of osteocytes die, does this secretion reverse, and osteoclasts become active [ 34 ]. …

Bridging the Gap in Understanding Bone Metastasis: A Multifaceted Perspective.

The treatment of patients with advanced cancer poses clinical problems due to the complications that arise as the disease progresses. Bone metastases are a common problem that cancer patients may face, and currently, there are no effective drugs to treat these individuals. Prostate, breast, and lung cancers often spread to the bone, causing significant and disabling health conditions. The bone is a highly active and dynamic tissue and is considered a favorable environment for the growth of cancer. The role of osteoblasts and osteoclasts in the process of bone remodeling and the way in which th

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… This network enables osteocytes to sense mechanical stimuli and transmit cellular signals to other osteocytes and osteoblasts on the bone surface [ 24 ]. This allows osteocytes to regulate osteoblast and osteoclast activity. … In the same myeloma model, osteocytes were shown to upregulate the expression of RANKL via Notch signaling, which, when inhibited, reduced osteocyte-induced RANKL upregulation [ 121 ]. …

Bone Metastasis Pain, from the Bench to the Bedside.

Bone is the most frequent site of metastasis of the most common cancers in men and women. Bone metastasis incidence has been steadily increasing over the years, mainly because of higher life expectancy in oncologic patients. Although bone metastases are sometimes asymptomatic, their consequences are most often devastating, impairing both life quality and expectancy, due to the occurrence of the skeletal-related events, including bone fractures, hypercalcemia and spinal cord compression. Up to 75% of patients endure crippling cancer-induced bone pain (CIBP), against which we have very few weapo

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… This amazing and quite exclusive property, called bone remodelling, can be accomplished by means of three resident cell types: osteocytes, osteoblasts and osteoclasts [ 1 ]. Osteocytes are the most abundant cell type in the bone, comprising more than 90% of bone cells [ 2 ]. … Osteocyte’s most recognised role is that of mechanosensors, but many other functions are emerging [ 3 ]. As an example, osteocytes can depose and resorb bone around them in particular conditions, such as hypercalcemia and lactation, respectively [ 3 , 4 ]. …

Myeloma Bone Disease: Update on Pathogenesis and Novel Treatment Strategies.

Bone disease, including osteolytic lesions and/or osteoporosis, is a common feature of multiple myeloma (MM). The consequences of skeletal involvement are severe pain, spinal cord compressions, and bone fractures, which have a dramatic impact on patients' quality of life and, ultimately, survival. During the past few years, several landmark studies significantly enhanced our insight into MM bone disease (MBD) by identifying molecular mechanisms leading to increased bone resorption due to osteoclast activation, and decreased bone formation by osteoblast inhibition. Bisphosphonates were the main

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… Osteocytes and adipocytes play an emerging role as MM-promoting cells in the bone niche. Osteocytes induce MM cell growth via direct activation of the Notch signaling pathway as well as increase in Notch receptor expression [ 35 ]. … In MBD, malignant plasma cells directly secrete RANKL and also stimulate its release via by T lymphocytes and osteocytes in the bone niche [ 56 ]. Specifically, MM cells induce osteocyte apoptosis via activation of Notch signaling, and apoptotic osteocytes express high levels of RANKL [ 35 , 54 ]. …

Mechanism of Action of Bortezomib and the New Proteasome Inhibitors on Myeloma Cells and the Bone Microenvironment: Impact on Myeloma-Induced Alterations of Bone Remodeling.

Multiple myeloma (MM) is characterized by a high capacity to induce alterations in the bone remodeling process. The increase in osteoclastogenesis and the suppression of osteoblast formation are both involved in the pathophysiology of the bone lesions in MM. The proteasome inhibitor (PI) bortezomib is the first drug designed and approved for the treatment of MM patients by targeting the proteasome. However, recently novel PIs have been developed to overcome bortezomib resistance. Interestingly, several preclinical data indicate that the proteasome complex is involved in both osteoclast and ost

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… In particular, living osteocytes produce soluble factors that inhibit osteoclast formation, whereas the apoptotic or autophagic osteocytes lose this inhibitory effect and promote bone resorption [ 46 ]. … The amazing osteocyte. Journal of Bone and Mineral Research. 2011;26(2):229–238. doi: 10.1002/jbmr.320. 44. Noble B. S., Reeve J. Osteocyte function, osteocyte death and bone fracture resistance. Molecular and Cellular Endocrinology. 2000;159(1-2):7–13. doi: 10.1016/S0303-7207(99)00174-4. 45. …

Role of bone-anabolic agents in the treatment of breast cancer bone metastases.

Skeletal metastases are an incurable complication afflicting the majority of patients who die from advanced breast cancer. They are most often osteolytic, characterized by net bone destruction and suppressed new bone formation. Life expectancy from first diagnosis of breast cancer bone metastases is several years, during which time skeletal-related events - including pain, fracture, hypercalcemia, and spinal cord compression - significantly degrade quality of life. The bone marrow niche can also confer hormonal and chemo-resistance. Most treatments for skeletal metastases target bone-destroyin

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… Osteocytes are resistant to apoptosis, but their numbers are decreased in bone chronically exposed to myeloma cells. Maturation of late osteoblasts into osteocytes may be blocked by factors made by MM or breast cancer, or osteocytes may be reprogrammed by the local presence of tumor cells. … MM cells can cause osteocyte apoptosis and also contribute to increased osteolysis by stimulating osteocyte production of IL-11 [ 32 ]. …

Sensory nerves: A driver of the vicious cycle in bone metastasis?

Bone is one of the preferential target organs of cancer metastasis. Bone metastasis is associated with various complications, of which bone pain is most common and debilitating. The cancer-associated bone pain (CABP) is induced as a consequence of increased neurogenesis, reprogramming and axonogenesis of sensory nerves (SNs) in harmony with sensitization and excitation of SNs in response to the tumor microenvironment created in bone. Importantly, CABP is associated with increased mortality, of which precise cellular and molecular mechanism remains poorly understood. Bone is densely innervated

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… Although the role of osteocytes in SN excitation and CABP induction during the progression of bone metastasis is currently unknown, morphological and anatomical features of osteocytes suggest that osteocytes may be involved in the pathophysiology of CABP induction. … Osteocytes are embedded in mineralized bone extending dendritic processes, which resemble SN axons, to communicate with other osteocytes. …

Clinical and Histopathological Aspects of MRONJ in Cancer Patients.

Medication-related osteonecrosis of the jaw (MRONJ) is a major complication of bisphosphonate treatment in cancer patients, and its etiology is not completely clarified. The study's goal is to find connections between the clinical and histopathological characteristics of osteonecrosis and bisphosphonates in a cohort of cancer patients who had osteonecrosis treated surgically. The retrospective study includes 51 patients of both sexes, aged 46 to 85 years, who underwent surgical treatment for MRONJ in two oral and maxillofacial surgery clinics (Craiova and Constanța). Demographic, clinical, and

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… In certain regions, osteocytes detect mechanical strain on the bone and send bone resorption signals [ 50 , 51 , 52 ]. … Although the apoptosis of osteocytes is essential for replacing the damaged bone [ 54 ], in the aged bone it does not take place normally, so bone homeostasis is regulated through the senescent osteocytes that increase their number of dendritic processes [ 32 , 55 ]. …