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  1. Article: Osteocytes: New Kids on the Block for Cancer in Bone Therapy.

    Anloague, Aric / Delgado-Calle, Jesus

    Cancers

    2023  Volume 15, Issue 9

    Abstract: The tumor microenvironment plays a central role in the onset and progression of cancer in the bone. Cancer cells, either from tumors originating in the bone or from metastatic cancer cells from other body systems, are located in specialized niches where ... ...

    Abstract The tumor microenvironment plays a central role in the onset and progression of cancer in the bone. Cancer cells, either from tumors originating in the bone or from metastatic cancer cells from other body systems, are located in specialized niches where they interact with different cells of the bone marrow. These interactions transform the bone into an ideal niche for cancer cell migration, proliferation, and survival and cause an imbalance in bone homeostasis that severely affects the integrity of the skeleton. During the last decade, preclinical studies have identified new cellular mechanisms responsible for the dependency between cancer cells and bone cells. In this review, we focus on osteocytes, long-lived cells residing in the mineral matrix that have recently been identified as key players in the spread of cancer in bone. We highlight the most recent discoveries on how osteocytes support tumor growth and promote bone disease. Additionally, we discuss how the reciprocal crosstalk between osteocytes and cancer cells provides the opportunity to develop new therapeutic strategies to treat cancer in the bone.
    Language English
    Publishing date 2023-05-07
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15092645
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  2. Article: Editorial: The role of the bone marrow microenvironment in multiple myeloma evolution and therapy.

    Schinke, Carolina / Weinhold, Niels / Delgado-Calle, Jesus

    Frontiers in oncology

    2023  Volume 13, Page(s) 1157555

    Language English
    Publishing date 2023-02-21
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2023.1157555
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  3. Article ; Online: Doubling Down on Wnt Signaling to Overcome Myeloma Bone Disease.

    Delgado-Calle, Jesús / Roodman, G David

    Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

    2023  Volume 38, Issue 6, Page(s) 812–813

    MeSH term(s) Humans ; Wnt Signaling Pathway ; Multiple Myeloma ; Wnt Proteins ; Bone Diseases ; Cell Line, Tumor
    Chemical Substances Wnt Proteins
    Language English
    Publishing date 2023-06-05
    Publishing country United States
    Document type Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Comment
    ZDB-ID 632783-7
    ISSN 1523-4681 ; 0884-0431
    ISSN (online) 1523-4681
    ISSN 0884-0431
    DOI 10.1002/jbmr.4863
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  4. Article ; Online: Role of Osteocytes in Cancer Progression in the Bone and the Associated Skeletal Disease.

    Adhikari, Manish / Delgado-Calle, Jesús

    Current osteoporosis reports

    2021  Volume 19, Issue 3, Page(s) 247–255

    Abstract: Purpose of review: The goal of this manuscript is to review the current knowledge on the role of osteocytes in cancer in the bone, discuss the potential of osteocytes as a therapeutic target, and propose future research needed to understand the ... ...

    Abstract Purpose of review: The goal of this manuscript is to review the current knowledge on the role of osteocytes in cancer in the bone, discuss the potential of osteocytes as a therapeutic target, and propose future research needed to understand the crosstalk between cancer cells and osteocytes in the tumor niche.
    Recent findings: Numerous studies have established that cancer cells manipulate osteocytes to facilitate invasion and tumor progression in bone. Moreover, cancer cells dysregulate osteocyte function to disrupt physiological bone remodeling, leading to the development of bone disease. Targeting osteocytes and their derived factors has proven to effectively interfere with the progression of cancer in the bone and the associated bone disease. Osteocytes communicate with cancer cells and are also part of the vicious cycle of cancer in the bone. Additional studies investigating the role of osteocytes on metastases to the bone and the development of drug resistance are needed.
    MeSH term(s) Animals ; Bone Diseases/pathology ; Bone Remodeling ; Disease Progression ; Humans ; Neoplasm Invasiveness/pathology ; Osteocytes/pathology ; Signal Transduction
    Language English
    Publishing date 2021-04-05
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2186581-4
    ISSN 1544-2241 ; 1544-1873
    ISSN (online) 1544-2241
    ISSN 1544-1873
    DOI 10.1007/s11914-021-00679-7
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  5. Article ; Online: The osteocyte as a signaling cell.

    Delgado-Calle, Jesus / Bellido, Teresita

    Physiological reviews

    2021  Volume 102, Issue 1, Page(s) 379–410

    Abstract: Osteocytes, former osteoblasts encapsulated by mineralized bone matrix, are far from being passive and metabolically inactive bone cells. Instead, osteocytes are multifunctional and dynamic cells capable of integrating hormonal and mechanical signals and ...

    Abstract Osteocytes, former osteoblasts encapsulated by mineralized bone matrix, are far from being passive and metabolically inactive bone cells. Instead, osteocytes are multifunctional and dynamic cells capable of integrating hormonal and mechanical signals and transmitting them to effector cells in bone and in distant tissues. Osteocytes are a major source of molecules that regulate bone homeostasis by integrating both mechanical cues and hormonal signals that coordinate the differentiation and function of osteoclasts and osteoblasts. Osteocyte function is altered in both rare and common bone diseases, suggesting that osteocyte dysfunction is directly involved in the pathophysiology of several disorders affecting the skeleton. Advances in osteocyte biology initiated the development of novel therapeutics interfering with osteocyte-secreted molecules. Moreover, osteocytes are targets and key distributors of biological signals mediating the beneficial effects of several bone therapeutics used in the clinic. Here we review the most recent discoveries in osteocyte biology demonstrating that osteocytes regulate bone homeostasis and bone marrow fat via paracrine signaling, influence body composition and energy metabolism via endocrine signaling, and contribute to the damaging effects of diabetes mellitus and hematologic and metastatic cancers in the skeleton.
    MeSH term(s) Animals ; Bone Remodeling/physiology ; Bone Resorption/metabolism ; Cell Differentiation/physiology ; Humans ; Osteoclasts/cytology ; Osteocytes/cytology ; Osteogenesis/physiology
    Language English
    Publishing date 2021-08-02
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 209902-0
    ISSN 1522-1210 ; 0031-9333
    ISSN (online) 1522-1210
    ISSN 0031-9333
    DOI 10.1152/physrev.00043.2020
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  6. Article ; Online: Ex Vivo Organ Cultures as Models to Study Bone Biology.

    Bellido, Teresita / Delgado-Calle, Jesus

    JBMR plus

    2020  Volume 4, Issue 3

    Abstract: The integrity of the skeleton is maintained by the coordinated and balanced activities of the bone cells. Osteoclasts resorb bone, osteoblasts form bone, and osteocytes orchestrate the activities of osteoclasts and osteoblasts. A variety of in vitro ... ...

    Abstract The integrity of the skeleton is maintained by the coordinated and balanced activities of the bone cells. Osteoclasts resorb bone, osteoblasts form bone, and osteocytes orchestrate the activities of osteoclasts and osteoblasts. A variety of in vitro approaches has been used in an attempt to reproduce the complex in vivo interactions among bone cells under physiological as well as pathological conditions and to test new therapies. Most cell culture systems lack the proper extracellular matrix, cellular diversity, and native spatial distribution of the components of the bone microenvironment. In contrast, ex vivo cultures of fragments of intact bone preserve key cell-cell and cell-matrix interactions and allow the study of bone cells in their natural 3D environment. Further, bone organ cultures predict the in vivo responses to genetic and pharmacologic interventions saving precious time and resources. Moreover, organ cultures using human bone reproduce human conditions and are a useful tool to test patient responses to therapeutic agents. Thus, these ex vivo approaches provide a platform to perform research in bone physiology and pathophysiology. In this review, we describe protocols optimized in our laboratories to establish ex vivo bone organ cultures and provide technical hints and suggestions. In addition, we present examples on how this technical approach can be employed to study osteocyte biology, drug responses in bone, cancer-induced bone disease, and cross-talk between bone and other organs © 2020 The Authors.
    Language English
    Publishing date 2020-02-14
    Publishing country England
    Document type Journal Article ; Review
    ISSN 2473-4039
    ISSN (online) 2473-4039
    DOI 10.1002/jbm4.10345
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  7. Article ; Online: Osteoclasts Control Lipid Secretion to Regulate Breast Cancer Bone Metastasis.

    Delgado-Calle, Jesus

    Endocrinology

    2017  Volume 158, Issue 3, Page(s) 458–460

    Language English
    Publishing date 2017-03-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 427856-2
    ISSN 1945-7170 ; 0013-7227
    ISSN (online) 1945-7170
    ISSN 0013-7227
    DOI 10.1210/en.2017-00036
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  8. Article ; Online: Osteocytes and Paget's Disease of Bone.

    Tenshin, Hirofumi / Delgado-Calle, Jesus / Windle, Jolene J / Roodman, G David / Chirgwin, John M / Kurihara, Noriyoshi

    Current osteoporosis reports

    2024  

    Abstract: Purpose of review: To describe the contributions of osteocytes to the lesions in Paget's disease, which are characterized by locally overactive bone resorption and formation.: Recent findings: Osteocytes, the most abundant cells in bone, are altered ... ...

    Abstract Purpose of review: To describe the contributions of osteocytes to the lesions in Paget's disease, which are characterized by locally overactive bone resorption and formation.
    Recent findings: Osteocytes, the most abundant cells in bone, are altered in Paget's disease lesions, displaying increased size, decreased canalicular length, incomplete differentiation, and less sclerostin expression compared to controls in both patients and mouse models. Pagetic lesions show increased senescent osteocytes that express RANK ligand, which drives osteoclastic bone resorption. Abnormal osteoclasts in Paget's disease secrete abundant IGF1, which enhances osteocyte senescence, contributing to lesion formation. Recent data suggest that osteocytes contribute to lesion formation in Paget's disease by responding to high local IGF1 released from abnormal osteoclasts. Here we describe the characteristics of osteocytes in Paget's disease and their role in bone lesion formation based on recent results with mouse models and supported by patient data.
    Language English
    Publishing date 2024-03-08
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2186581-4
    ISSN 1544-2241 ; 1544-1873
    ISSN (online) 1544-2241
    ISSN 1544-1873
    DOI 10.1007/s11914-024-00863-5
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  9. Article: The multifunctional role of Notch signaling in multiple myeloma.

    Sabol, Hayley M / Delgado-Calle, Jesus

    Journal of cancer metastasis and treatment

    2021  Volume 7

    Abstract: Multiple myeloma (MM) is a hematologic cancer characterized by uncontrolled growth of malignant plasma cells in the bone marrow and currently is incurable. The bone marrow microenvironment plays a critical role in MM. MM cells reside in specialized ... ...

    Abstract Multiple myeloma (MM) is a hematologic cancer characterized by uncontrolled growth of malignant plasma cells in the bone marrow and currently is incurable. The bone marrow microenvironment plays a critical role in MM. MM cells reside in specialized niches where they interact with multiple marrow cell types, transforming the bone/bone marrow compartment into an ideal microenvironment for the migration, proliferation, and survival of MM cells. In addition, MM cells interact with bone cells to stimulate bone destruction and promote the development of bone lesions that rarely heal. In this review, we discuss how Notch signals facilitate the communication between adjacent MM cells and between MM cells and bone/bone marrow cells and shape the microenvironment to favor MM progression and bone disease. We also address the potential and therapeutic approaches used to target Notch signaling in MM.
    Language English
    Publishing date 2021-04-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2819994-7
    ISSN 2394-4722
    ISSN 2394-4722
    DOI 10.20517/2394-4722.2021.35
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  10. Article ; Online: New Insights Into the Local and Systemic Functions of Sclerostin: Regulation of Quiescent Bone Lining Cells and Beige Adipogenesis in Peripheral Fat Depots.

    Delgado-Calle, Jesus / Bellido, Teresita

    Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

    2017  Volume 32, Issue 5, Page(s) 889–891

    MeSH term(s) Adipocytes ; Adipogenesis ; Osteoblasts ; Osteocytes
    Language English
    Publishing date 2017-04-06
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Comment
    ZDB-ID 632783-7
    ISSN 1523-4681 ; 0884-0431
    ISSN (online) 1523-4681
    ISSN 0884-0431
    DOI 10.1002/jbmr.3141
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