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Androgen Receptor-CaMKK2 Axis in Prostate Cancer and Bone Microenvironment.

The skeletal system is of paramount importance in advanced stage prostate cancer (PCa) as it is the preferred site of metastasis. Complex mechanisms are employed sequentially by PCa cells to home to and colonize the bone. Bone-resident PCa cells then recruit osteoblasts (OBs), osteoclasts (OCs), and macrophages within the niche into entities that promote cancer cell growth and survival. Since PCa is heavily reliant on androgens for growth and survival, androgen-deprivation therapy (ADT) is the standard of care for advanced disease. Although it significantly improves survival rates, ADT detrime

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… Recent studies from multiple myeloma highlight the importance of osteocytes, the most abundant bone cells, in tumor-bone interactions ( 34 ). … Tumor-induced pressure in the bone microenvironment causes osteocytes to promote the growth of prostate cancer bone metastases . …

Chronic Pain and Bone-Related Pathologies: A Narrative Review.

PurposePain related to bone may occur as a result of trauma, bone fracture, genetic disease, arthritis, benign or malignant primary bone tumors and bone cancer metastases. We discuss the pathophysiology of chronic bone-related pain, treatment options and therapeutic perspectives.MethodsUsing predefined terms, we searched PubMed, MEDLINE, and Google Scholar for meta-analyses, evidence-based reviews, and clinical practice guidelines. This narrative article reviews pathologies linked to chronic bone pain and discusses the preventive and therapeutic strategies for better bone pain management.Resul

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… Osteocytes, that are very abundant in bone, are also implicated, as osteocyte-related cytokines like tumor necrosis factor (TNFα) regulate osteoclast formation by enhancing receptor activator nuclear factor kB ligand (RANKL) and sclerostin, and inflammatory cytokines have osteoclastogenic effects. … For example, inhibitors of Cathepsin K, the proteolytic enzyme produced by osteoclasts, have been shown in animal models to exhibit modest chondroprotective and pain-reducing effects. 57 Sclerostin, produced by osteocytes, prevents bone formation by inhibiting Wnt signaling in the cells: antisclerostin …

ACY‑1215, a HDAC6 inhibitor, decreases the dexamethasone‑induced suppression of osteogenesis in MC3T3‑E1 cells.

Glucocorticoid‑induced osteoporosis is the commonest form of drug‑induced osteoporosis. Histone deacetylase 6 (HDAC6) is involved in the differentiation from mesenchymal stem cells to osteoblasts. However, the role of ricolinostat (ACY‑1215, HDAC6 inhibitor) in the dexamethasone (Dex)‑induced proliferation and differentiation of preosteoblasts remains to be elucidated. The protein expression and mRNA expression levels of HDAC6, osteopontin (OPN), runt‑related transcription factor 2 (Runx2), osterix (Osx), collagen I (COL1A1) and glucocorticoid receptor (GR) in MC3T3‑E1 cells were analyzed by w

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… GR has multiple effects on osteocytes in osteoporosis; however, these have been only rarely investigated ( 28 ). Plotkin et al ( 29 ) demonstrated that GCs mediate the apoptosis of bone cells via GR. … osteoarthritic osteoblasts Biomed Pharmacother 118 109357 2019 10.1016/j.biopha.2019.109357 31548177 28 Komori T Regulation of skeletal development by the Runx family transcription factors J Cell Biochem 95 445 453 2005 10.1002/jcb.20420 15786491 29 Plotkin L Manolagas S Bellido T Glucocorticoids induce osteocyte …

Skeletal Site-specific Effects of Zoledronate on in vivo Bone Remodeling and in vitro BMSCs Osteogenic Activity.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) has been associated with long-term oral or intravenous administration of nitrogen-containing bisphosphonates (BPs). However, the pathogenesis of BRONJ remains unknown, and definitively effective treatment has not yet been established. Bisphosphonate-related osteonecrosis (BRON) tends to occur in maxillofacial bones. Why this occurs is still unclear. Here we show that zoledronate (Zol) treatment suppresses alveolar bone remodeling after tooth typical clinical and radiographic hallmarks of the human BRONJ, whereas enhances peripheral bone q

Exosomes to exosome-functionalized scaffolds: a novel approach to stimulate bone regeneration.

Bone regeneration is a complex biological process that relies on the orchestrated interplay of various cellular and molecular events. Bone tissue engineering is currently the most promising method for treating bone regeneration. However, the immunogenicity, stable and cell quantity of seed cells limited their application. Recently, exosomes, which are small extracellular vesicles released by cells, have been found to effectively address these problems and better induce bone regeneration. Meanwhile, a growing line of research has shown the cargos of exosomes may provide effective therapeutic an

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… Exosomes effect on different cells during bone regeneration Bone regeneration is a complex process involving a variety of cells, including osteoblasts, osteoclasts, chondrocytes, osteocytes, and immune cells. … Effect of donor cell derived exosomes act on osteogenesis-related cells, including MSCs, osteoblasts, osteoclasts, chondrocytes, osteocytes, chondroblast, vascular endothelial cell, and the local immune microenvironment composed of macrophages, etc. …

Extracellular vesicles in multiple myeloma-bone marrow niche crosstalk: from cellular dialogue to clinical perspectives.

Multiple myeloma (MM) is a haematological neoplasia defined by the clonal expansion of malignant plasma cells within the intricate and dynamic ecosystem of the bone marrow (BM). Although genetic aberrations intrinsic to tumour cells play a critical role in MM initiation, the advancement and aggressiveness of the disease are heavily influenced by ongoing signalling exchanges and persistent interactions with the surrounding microenvironment. Extracellular vesicles (EVs) are increasingly recognized as essential messengers in this reciprocal communication, acting as membrane-encapsulated vehicles

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… Furthermore, the cross-talk between osteocytes and MM cells, orchestrated by osteocyte-secreted exosomal miRNAs, affects MM therapeutic response. … In this context, a pivotal role of exosomal miR-483-3p and miR-513a-5p has been suggested, which, once transferred from osteocytes to MM cells, support the acquisition of MM cell stem-like phenotype by activating the HIF-1α signalling [ 94 ]. …

Balancing the Scales: The Dual Role of Interleukins in Bone Metastatic Microenvironments.

Bone metastases, a common and debilitating consequence of advanced cancers, involve a complex interplay between malignant cells and the bone microenvironment. Central to this interaction are interleukins (ILs), a group of cytokines with critical roles in immune modulation and inflammation. This review explores the dualistic nature of pro-inflammatory and anti-inflammatory interleukins in bone metastases, emphasizing their molecular mechanisms, pathological impacts, and therapeutic potential. Pro-inflammatory interleukins, such as IL-1, IL-6, and IL-8, have been identified as key drivers in pro

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… Additionally, IL-6 produced by osteocytes under mechanical loading influences osteoblast differentiation and osteoclast activity via the JAK/STAT3 and ERK signaling pathways [ 67 ]. … Furthermore, IL-6 can modulate osteocyte communication towards osteoclasts and osteoblasts, affecting bone mass by regulating gene expression involved in osteoclastogenesis and osteoblast differentiation [ 68 ]. …

Roles of LINC01473 and CD74 in osteoblasts in multiple myeloma bone disease.

The suppression of osteoblast (OB) activity is partially responsible for multiple myeloma (MM) bone disease. Long non-coding RNAs (lncRNAs) play a vital role in bone formation and resorption. However, their functions in OBs from patients with MM have rarely been reported. Through high-throughput sequencing of OBs from patients with MM and healthy controls, we identified several lncRNAs and messenger RNAs (mRNAs) with different expression profile and validated them using quantitative real-time PCR. In total, 22 upregulated and 21 downregulated lncRNAs were found in OBs from patients with MM. Mo

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… Overactive osteoclast and reduced osteoblast (OB) activities are responsible for pathological bone remodeling. 3 MM cells and osteocytes restrained OB activity by expressing wingless-type antagonists such as sclerostin, Dickkopf-1, and soluble frizzled-related proteins. 4 5 Furthermore, activin-A, semaphorin … 4D, and cytokines (secreted by bone marrow stromal cells, MM cells, osteoclasts, and immune cells) suppressed OB production, differentiation, and function. 6–8 Long non-coding RNAs (lncRNAs) play an important role in the development and maintenance of cellular phenotypes, including chondrocytes and osteocytes …

Postmenopausal women with osteoarthritis and osteoporosis show different ultrastructural characteristics of trabecular bone of the femoral head.

BackgroundOsteoporosis (OP) and osteoarthritis (OA) are public health diseases affecting the quality of life of the elderly, and bring about a heavy burden to the society and family of patients. It has been debated whether or not there is an inverse relationship between these two disorders.MethodsTo compare the exact difference in bone tissue structure between osteoporosis and osteoarthritis, we observed the ultrastructure of trabecular bone from the femoral heads using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). A total of 15 femoral head specimens from post

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… TEM In the OP group, some collagen fibers were found in regular arrays, while others appeared disorderly with almost no osteocytes observed, even under high magnification (Fig. 5A, 5B ). … No osteocytes could be seen in the trabecular bone of femoral head in women with OP. (×3400) (×5800). C. Loose collagen fibrils on the edge of the trabecular bone. (×3400). D. Osteoblasts with depressed function floated on the surface of the bone. …

Bone Loss, Osteoporosis, and Skeletal Fragility: Hidden Consequences of Cancer Cachexia.

Cancer cachexia (CC) is a devastating, multi-organ syndrome historically defined by the progressive wasting of skeletal muscle and adipose tissue. However, emerging evidence suggests that the skeletal system is also a major, yet underappreciated target of this catabolic state. While bone loss in oncology is primarily attributed to skeletal metastasis or cancer treatment-induced bone loss (CTIBL), clinical and preclinical data has increasingly demonstrated that tumor and host-derived systemic signals can drive severe bone deterioration even in non-metastatic disease. This review synthesizes cur

New players in the landscape of renal cell carcinoma bone metastasis and therapeutic opportunities.

Approximately one-third of advanced renal cell carcinoma (RCC) patients develop osteolytic bone metastases, leading to skeletal complications. In this review, we first provide a comprehensive perspective of seminal studies on bone metastasis of RCC describing the main molecular modulators and growth factor signaling pathways most important for the RCC-stimulated osteoclast-mediated bone destruction. We next focus on newer developments revealing with in-depth details, the bidirectional interplay between renal cancer cells and the immune and stromal microenvironment that can through epigenetic r

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… METASTASIS Bone, comprising 60% inorganic material like calcium and phosphate, 25% organic material primarily collagen type I and 5% water, serves multiple functions like structural support and organ protection. 14 It is a complex tissue composed of four cell types: osteoblasts, bone lining cells, osteocytes … Osteoblasts have three different fate: apoptosis, differentiation into osteocytes, or transformation into bone lining cells. 16 Bone lining cells are quiescent osteoblasts covering the bone, while osteocytes, representing 90% of all bone cells, maintain the balance between bone resorption and formation …

Reviewing the Significance of Vitamin D Substitution in Monoclonal Gammopathies.

Vitamin D is a steroid hormone that is essential for bone mineral metabolism and it has several other effects in the body, including anti-cancer actions. Vitamin D causes a reduction in cell growth by interrupting the cell cycle. Moreover, the active form of vitamin D, i.e., 1,25-dihydroxyvitamin D, exerts various effects via its interaction with the vitamin D receptor on the innate and adaptive immune system, which could be relevant in the onset of tumors. Multiple myeloma is a treatable but incurable malignancy characterized by the growth of clonal plasma cells in protective niches in the bo

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… It suppresses PTH and increases the expression of the osteocyte-specific hormone fibroblast growth factor 23 (FGF23), which is a marker of osteocytes in the early phase of secondary mineralization [ 3 ]. … Vitamin D sterols increase FGF23 expression by stimulating osteoblast and osteocyte maturation in CKD bone. Bone. 2019;127:626–634. doi: 10.1016/j.bone.2019.07.026. 5. Masuyama R. Role of local vitamin D signaling and cellular calcium transport system in bone homeostasis. J. Bone Min. …

Beyond boundaries: unraveling innovative approaches to combat bone-metastatic cancers.

Evidence demonstrated that bones, liver, and lungs are the most common metastasis sites in some human malignancies, especially in prostate and breast cancers. Bone is the third most frequent target for spreading tumor cells among these organs and tissues. Patients with bone-metastatic cancers face a grim prognosis characterized by short median survival time. Current treatments have proven insufficient, as they can only inhibit metastasis or tumor progression within the bone tissues rather than providing a curative solution. Gaining a more profound comprehension of the interplay between tumor c

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… Embedded osteocytes in the mineral of the bone play a role as mechanosensors and communicate via gap junctions and dendrites to regulate osteoclasts’ and osteoblasts’ actions. In addition to producing bone remodeling cytokines, osteocytes produce other essential mediators. … Furthermore, Dickkopf-related proteins 1 (DKK1) and sclerostin are released by osteocytes, inhibiting osteoblastogenesis from MSCs by suppressing WNT signaling. …

Cutting edge developments in bone oncology - Highlights from the Cancer and Bone Society 2024 annual meeting.

The 2024 Annual Conference of the Cancer and Bone Society (CABS), held jointly with the Bone Research Society at the University of Sheffield, highlighted the Society's enduring mission to advance understanding of cancer-bone interactions through collaboration, mentorship, and scientific excellence. Established from the early Cancer Induced Bone Disease meetings and re-emerging as an independent body in 2016, CABS continues to serve as a global community bridging basic, translational, and clinical research. This year's meeting featured a comprehensive scientific program spanning tumor-bone biol

Targeting NOTCH3 to eradicate dormant and therapy-resistant multiple myeloma cells.

BackgroundDespite significant therapeutic advances, multiple myeloma (MM) remains incurable in most patients due to frequent tumor relapse. A major contributor to relapse is clonal heterogeneity, where subclones exhibit distinct mechanisms of therapy resistance, along with the presence of drug-resistant dormant cells. Eliminating these distinct populations, which often coexist in the tumor niche, is clinically challenging. Identifying survival mechanisms shared by drug-resistant proliferating and dormant cells holds potential for the simultaneous elimination of different tumor-repopulating clo

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… Novel CCL3-HMGB1 signaling axis regulating osteocyte RANKL expression in multiple myeloma. Haematologica. 2025;110(4):952–66. 23. Kaur J, Adhikari M, Sabol HM, Anloague A, Khan S, Kurihara N, et al. … Notch3 signaling between myeloma cells and osteocytes in the tumor niche promotes tumor growth and bone destruction. Neoplasia. 2022;28:100785. 26. Sabol HM, Anloague A, Kaur J, Bustamante-Gomez C, Khan S, Paxton BC, et al. …

Bone health in cancer: perspective on the use of osteoanabolic agents.

Cancer negatively impacts bone health through various mechanisms, including treatment-induced bone loss and malignant bone lesions, often leading to increased fracture risk and higher morbidity and mortality. Antiresorptive agents (bisphosphonates and denosumab) are the current standard of care to reduce the risk of skeletal-related events and prevent treatment-related fragility fractures in patients with cancer. While there is strong evidence to support their benefits in cancer, there is potential room for further reduction in the risk of pathologic and fragility fractures. This narrative rev

Interactions between cancer cells and bone microenvironment promote bone metastasis in prostate cancer.

Bone metastasis is the leading cause of death in prostate cancer patients, for which there is currently no effective treatment. Since the bone microenvironment plays an important role in this process, attentions have been directed to the interactions between cancer cells and the bone microenvironment, including osteoclasts, osteoblasts, and bone stromal cells. Here, we explained the mechanism of interactions between prostate cancer cells and metastasis-associated cells within the bone microenvironment and further discussed the recent advances in targeted therapy of prostate cancer bone metasta

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… Since osteoblasts express AR, and the expression of AR increases during osteoblast maturation into osteocyte, it is possible that androgen may also be involved in bone metastasis [ 65 ]. … IL-6 exhibits both cis- and trans-signaling in osteocytes and osteoblasts, but only trans-signaling promotes bone formation and osteoclastogenesis. J Biol Chem. 2019;294(19):7850–7863. doi: 10.1074/jbc.RA119.008074. 79. Rao S, Cronin SJF, Sigl V, Penninger JM. …

Contribution of immune cells to bone metastasis pathogenesis.

Bone metastasis is closely related to the survival rate of cancer patients and reduces their quality of life. The bone marrow microenvironment contains a complex immune cell component with a local microenvironment that is conducive to tumor formation and growth. In this unique immune environment, a variety of immune cells, including T cells, natural killer cells, macrophages, dendritic cells, and myeloid-derived suppressor cells, participate in the process of bone metastasis. In this review, we will introduce the interactions between immune cells and cancer cells in the bone microenvironment,

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… The formation and evolution of bone metastasis include involved communication occurring among tumor cells, immune cells, and osteocytes ( 2 ). … Conclusions In conclusion, the complex interactions among tumor cells, immune cells, and osteocytes in the spinal marrow microenvironment demand further research into the mechanisms that trigger bone metastasis. …

Nanogel-Based Precision Bone Regeneration: Rational Design, Biological Barrier Penetration, and Osteoporotic Microenvironment Remodeling.

The pathogenesis of osteoporosis is primarily associated with impaired communication between osteoblasts and osteoclasts, leading to disrupted bone homeostasis. Conventional biomaterials mainly rely on macroscopic structural support and are limited in their ability to precisely regulate the complex bone microenvironment and overcome biological barriers. As representative soft matter nanoplatforms, nanogels possess unique viscoelastic mechanical properties and adaptive biointerfacial properties, offering new opportunities to overcome physical barriers within bone tissues. Moving beyond previous

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… This enables them to pass through the osteocyte LCS (approximately 100–300 nm in diameter). … As a result, they shift from surface deposition to deep penetration into the bone matrix, where they can directly interact with osteocytes and bone marrow immune cells. 14 , 15 However, penetration ability does not necessarily indicate effective delivery. …

" Нанотехнология " : новые стратегии для многократной терапии миеломы.

Достижения в области нанотехнологии открыли новые возможности для диагностики и лечения множественной миеломы (ММ), гематологической злокачественности, характеризующейся клональным распространением плазменных клеток в костном мозге. В этом обзоре раскрывается потенциал нанотехнологии для революции миэломы с уделением особого внимания системам доставки наркотиков наночастиц, методам наномасштабной съемки и наноиммунотерапии. Системы доставки наркотиков, основанные на нанопартии, обеспечивают повышенную целенаправленность наркотиков, снижение системной токсичности и повышение терапевтической эфф

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… Another study investigates osteocyte involvement in the pathogenesis of bone lesions and osteoclast (OCL) activation in multiple myeloma (MM). Findings indicate a significant reduction in viable osteocytes in MM patients, particularly those with bone lesions, where increased apoptosis is evident. … These results highlight a potential mechanistic link between reduced osteocyte viability and MM-related bone complications, suggesting a new avenue for therapeutic exploration [ 16 ]. The current standard of care for multiple myeloma is complex and typically involves a multimodal approach. …