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Advances in Osteoimmunology and Bone Biology
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Advances in Osteoimmunology and Bone Biology

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (31 August 2022) | Viewed by 10797

Special Issue Editors

Dr. Gabriela Loots

E-Mail Website
Guest Editor
Department of Orthopaedic Surgery, University of California Davis Health, Sacramento, CA, USA
Interests: bone and cartilage biology; osteoarthritis; post-traumatic osteoarthritis; Wnt signaling; cancer metastasis
Special Issues, Collections and Topics in MDPI journals
Dr. Jennifer O. Manilay

E-Mail Website
Guest Editor
Department of Molecular and Cell Biology, School of Natural Sciences, University of California, Merced, CA, USA
Interests: immunology; stem cell biology; hematopoiesis; skeletal biology
Special Issues, Collections and Topics in MDPI journals
Dr. Nadia Rucci

E-Mail Website
Guest Editor
Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, Italy
Interests: bone; osteopetrosis; osteoporosis; bone metastases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Traditionally, osteoimmunology investigated the molecular mechanisms underlying bone destruction associated with inflammatory diseases, and focused primarily on the role of osteoclasts in bone homeostasis. In recent years, it has become increasingly clear that other pathologic conditions and genetic deficiencies in immunomodulatory molecules also elicit skeletal phenotypes. The advent of OMIC approaches has also revealed that the immune and bone systems share many molecules, including cytokines, chemokines, transcription factors and signalling molecules and that bone cells reciprocally regulate immune cells and haematopoiesis. Here, we invite the submission of new studies that have explored the role of immune cells and immune cell-derived factors that control, regulate, or influence the function of osteoblasts, osteoclasts, and osteocytes. Similarly, we also seek studies where defects in molecules expressed primarily in skeletal cells, or alleles associated with skeletal phenotypes, reciprocally affect the development, persistence or behavior of immune cells in the bone marrow, or systemically.

Prof. Gabriela G. Loots
Dr. Jennifer O. Manilay
Dr. Nadia Rucci
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • osteoimmunology
  • bone marrow niche
  • hematopoiesis
  • high bone mass
  • low bone mass
  • osteoclast
  • osteoblast
  • osteocyte
  • cytokines
  • chemokines
  • immune modulation

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Published Papers (3 papers)

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24 pages, 4669 KiB  
Article
Sclerostin Depletion Induces Inflammation in the Bone Marrow of Mice
by Cristine Donham, Betsabel Chicana, Alexander G. Robling, Asmaa Mohamed, Sonny Elizaldi, Michael Chi, Brian Freeman, Alberto Millan, Deepa K. Murugesh, Nicholas R. Hum, Aimy Sebastian, Gabriela G. Loots and Jennifer O. Manilay
Int. J. Mol. Sci. 2021, 22(17), 9111; https://doi.org/10.3390/ijms22179111 - 24 Aug 2021
Cited by 7 | Viewed by 3932
Abstract
Romosozumab, a humanized monoclonal antibody specific for sclerostin (SOST), has been approved for treatment of postmenopausal women with osteoporosis at a high risk for fracture. Previous work in sclerostin global knockout (Sost−/−) mice indicated alterations in immune cell development in [...] Read more.
Romosozumab, a humanized monoclonal antibody specific for sclerostin (SOST), has been approved for treatment of postmenopausal women with osteoporosis at a high risk for fracture. Previous work in sclerostin global knockout (Sost−/−) mice indicated alterations in immune cell development in the bone marrow (BM), which could be a possible side effect in romosozumab-treated patients. Here, we examined the effects of short-term sclerostin depletion in the BM on hematopoiesis in young mice receiving sclerostin antibody (Scl-Ab) treatment for 6 weeks, and the effects of long-term Sost deficiency on wild-type (WT) long-term hematopoietic stem cells transplanted into older cohorts of Sost−/− mice. Our analyses revealed an increased frequency of granulocytes in the BM of Scl-Ab-treated mice and WT→Sost−/− chimeras, indicating myeloid-biased differentiation in Sost-deficient BM microenvironments. This myeloid bias extended to extramedullary hematopoiesis in the spleen and was correlated with an increase in inflammatory cytokines TNFα, IL-1α, and MCP-1 in Sost−/− BM serum. Additionally, we observed alterations in erythrocyte differentiation in the BM and spleen of Sost−/− mice. Taken together, our current study indicates novel roles for Sost in the regulation of myelopoiesis and control of inflammation in the BM. Full article
(This article belongs to the Special Issue Advances in Osteoimmunology and Bone Biology)
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13 pages, 2310 KiB  
Article
Bifunctional Role of CrkL during Bone Remodeling
by Jung Ha Kim, Kabsun Kim, Inyoung Kim, Semun Seong, Hyun Kook, Kyung Keun Kim, Jeong-Tae Koh and Nacksung Kim
Int. J. Mol. Sci. 2021, 22(13), 7007; https://doi.org/10.3390/ijms22137007 - 29 Jun 2021
Cited by 1 | Viewed by 2277
Abstract
Coupled signaling between bone-forming osteoblasts and bone-resorbing osteoclasts is crucial to the maintenance of bone homeostasis. We previously reported that v-crk avian sarcoma virus CT10 oncogene homolog-like (CrkL), which belongs to the Crk family of adaptors, inhibits bone morphogenetic protein 2 (BMP2)-mediated osteoblast [...] Read more.
Coupled signaling between bone-forming osteoblasts and bone-resorbing osteoclasts is crucial to the maintenance of bone homeostasis. We previously reported that v-crk avian sarcoma virus CT10 oncogene homolog-like (CrkL), which belongs to the Crk family of adaptors, inhibits bone morphogenetic protein 2 (BMP2)-mediated osteoblast differentiation, while enhancing receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclast differentiation. In this study, we investigated whether CrkL can also regulate the coupling signals between osteoblasts and osteoclasts, facilitating bone homeostasis. Osteoblastic CrkL strongly decreased RANKL expression through its inhibition of runt-related transcription factor 2 (Runx2) transcription. Reduction in RANKL expression by CrkL in osteoblasts resulted in the inhibition of not only osteoblast-dependent osteoclast differentiation but also osteoclast-dependent osteoblast differentiation, suggesting that CrkL participates in the coupling signals between osteoblasts and osteoclasts via its regulation of RANKL expression. Therefore, CrkL bifunctionally regulates osteoclast differentiation through both a direct and indirect mechanism while it inhibits osteoblast differentiation through its blockade of both BMP2 and RANKL reverse signaling pathways. Collectively, these data suggest that CrkL is involved in bone homeostasis, where it helps to regulate the complex interactions of the osteoblasts, osteoclasts, and their coupling signals. Full article
(This article belongs to the Special Issue Advances in Osteoimmunology and Bone Biology)
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10 pages, 694 KiB  
Opinion
RANKL-RANK-OPG Pathway in Charcot Diabetic Foot: Pathophysiology and Clinical-Therapeutic Implications
by Tommaso Greco, Antonio Mascio, Chiara Comisi, Chiara Polichetti, Silvio Caravelli, Massimiliano Mosca, Nicola Mondanelli, Elisa Troiano, Giulio Maccauro and Carlo Perisano
Int. J. Mol. Sci. 2023, 24(3), 3014; https://doi.org/10.3390/ijms24033014 - 3 Feb 2023
Cited by 13 | Viewed by 3454
Abstract
Charcot Foot (CF), part of a broader condition known as Charcot Neuro-Osteoarthropathy (CNO), is characterized by neuropathic arthropathy with a progressive alteration of the foot. CNO is one of the most devastating complications in patients with diabetes mellitus and peripheral neuropathy but can [...] Read more.
Charcot Foot (CF), part of a broader condition known as Charcot Neuro-Osteoarthropathy (CNO), is characterized by neuropathic arthropathy with a progressive alteration of the foot. CNO is one of the most devastating complications in patients with diabetes mellitus and peripheral neuropathy but can also be caused by neurological or infectious diseases. The pathogenesis is multifactorial; many studies have demonstrated the central role of inflammation and the Receptor Activator of NF-κB ligand (RANKL)-Receptor Activator of NF-κB (RANK)-Osteoprotegerin (OPG) pathway in the acute phase of the disease, resulting in the serum overexpression of RANKL. This overexpression and activation of this signal lead to increased osteoclast activity and osteolysis, which is a prelude to bone destruction. The aim of this narrative review is to analyze this signaling pathway in bone remodeling, and in CF in particular, to highlight its clinical aspects and possible therapeutic implications of targeting drugs at different levels of the pathway. Drugs that act at different levels in this pathway are anti-RANKL monoclonal antibodies (Denosumab), bisphosphonates (BP), and calcitonin. The literature review showed encouraging data on treatment with Denosumab, although in a few studies and in small sample sizes. In contrast, BPs have been re-evaluated in recent years in relation to the high possibility of side effects, while calcitonin has shown little efficacy on CNO. Full article
(This article belongs to the Special Issue Advances in Osteoimmunology and Bone Biology)
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