Relationship between abnormal osteoblasts and cellular immunity in multiple myeloma

Fu, Rong; Gao, Shan; Peng, Fengping; Li, Jing; Liu, Hui; Wang, Huaquan; Xing, Lu; Shao, Zonghong

doi:10.1186/1475-2867-14-62

Cited by 9 publications

(8 citation statements)

References 19 publications

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“…The OB activity was affected by a series of mechanisms including the abnormal production of cytokines, chemokines, and inflammatory factors, which usually increased in the marrow microenvironment [ 11 ]. Abnormal OBs were also proven associated with the imbalanced cellular immunity in MM [ 12 ]. Moreover, deregulated osteoblastogenesis was promoted by the direct OB interactions with the myeloma cells.…”

Section: Resultsmentioning

confidence: 99%

Osteoblast inhibition by chemokine cytokine ligand3 in myeloma-induced bone disease

Liu

Zhao

et al. 2014

Cancer Cell Int

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BackgroundMultiple myeloma is a hematologic malignancy characterized by the accumulation of monoclonal plasma cells in the bone marrow. A common manifestation of the disease is myeloma bone disease (MBD), which is caused by increased osteoclastic bone resorption and decreased bone formation. The chemokine cytokine ligand 3 (CCL3) is a pro-inflammatory protein and chemokine that stimulates osteoclasts in MBD. However, little is known about the effect of CCL3 on osteoblasts (OB).MethodsThe OBs are induced from patients with MBD and healthy donors, cultured in vitro, and identified by histochemistry. The effects of CCL3 and CCL3 antibody on the OBs in vitro are observed. The CCL3 receptor (CCR1), osteocalcin (OCN), runt-related transcription factor 2 (Runx2), and osterix (Osx) are detected using flow cytometry, enzyme-linked immunosorbent assay, and real-time PCR.ResultsProliferation and osteogenic potential of the OB in patients with MBD are suppressed. Moreover, the CCR1 expression is significantly higher in patients with MBD than in normal controls. The OCN level, quantity of calcium nodules, and Runx2 and Osx levels decrease after CCL3 stimulation, which indicates that CCL3 inhibits OB function. Furthermore, CCL3 antibody partially restores OB activity through the upregulation of the OCN, Runx2, and Osx.ConclusionsCCL3 contributes to the OB/OC imbalance by inhibiting OB differentiation and function in MBD.

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Section: Resultsmentioning

confidence: 99%

Osteoblast inhibition by chemokine cytokine ligand3 in myeloma-induced bone disease

Liu

Zhao

et al. 2014

Cancer Cell Int

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“…Bone formation and the immune system are closely associated through cellular and molecular interactions ( 18 ). The interaction of TIM3 with its ligand, Galectin-9, promotes apoptosis of T-helper 1 cells, and induces CD8 + T cell exhaustion with decreased production of interferon γ; it also induces the expansion of myeloid-derived suppressor cells, which suppress immune responses indirectly.…”

Section: Discussionmentioning

confidence: 99%

Abnormal changes in the quantity and function of osteoblasts cultured in�vitro in patients with myelodysplastic syndrome

et al. 2018

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Changes in bone marrow niches can lead to the occurrence of myelodysplastic syndrome (MDS). As an important part of the bone marrow niche, osteoblasts serve a key role in the progression of MDS. The present study investigated the quantity and function of osteoblasts and, through in vitro assays, detected changes in signaling pathways and the association with progression in MDS patients. The ratios of osteoprogenitors (CD34+OCN+) and OCN+CD34−Lin− osteoblasts in MDS patients were significantly less than those of normal controls. The results of this study demonstrated that the quantity and activity of osteoblasts in MDS patients were lower than those in normal controls. Furthermore the activity of osteoblasts in patients correlated with the severity of MDS. The quantity of osteoblasts cultured in vitro from high-risk and very high-risk MDS patients (WHO Classification-Based Prognostic Scoring System score 3–6) was decreased. The levels of T-cell immunoglobulin and mucin domain-containing 3 (TIM3) and Jagged 1 were also increased in the osteoblasts in vitro. These results indicated that osteoblasts are abnormally altered in MDS patients, and that there are associations between abnormal changes of osteoblasts and the severity of MDS.

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“…Regulatory T-cells and immunosuppressive myeloid-derived suppressor cells [73] are now being identified as important new targets that inhibit the immune response in multiple myeloma [74]. Interestingly, cellular immunity was found to be decreased in myeloma patients, including decreased ratio of CD4 + /CD8 + , DC1/DC2 and Th1/Th2 cells, as well as an increased ratio of regulatory T cells, and some of these metrics of immune function (CD4 + /CD8 + ratio and CD4 + CD25 + /CD3 + T ratio) were significantly positively correlated with the quantity of osteoblasts [75]. Hence, the potential effects of osteoblast loss on multiple myeloma via inhibition of the immune system require further investigation.…”

Section: Effects Of Osteoblasts On Multiple Myelomamentioning

confidence: 99%

Dynamic interplay between bone and multiple myeloma: Emerging roles of the osteoblast

Reagan

Liaw

Rosen

et al. 2015

Bone

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Multiple myeloma is a B-cell malignancy characterized by the unrelenting proliferation of plasma cells. Multiple myeloma causes osteolytic lesions and fractures that do not heal due to decreased osteoblastic and increased osteoclastic activity. However, the exact relationship between osteoblasts and myeloma cells remains elusive. Understanding the interactions between these dynamic bone-forming cells and myeloma cells is crucial to understanding how osteolytic lesions form and persist, and how tumors grow within the bone marrow. This review provides a comprehensive overview of basic and translational research focused on the role of osteoblasts in multiple myeloma progression and their relationship to osteolytic lesions. Importantly, current challenges for in vitro studies exploring direct osteoblastic effects on myeloma cells, and gaps in understanding the role of the osteoblast in myeloma progression are delineated. Finally, successes and challenges in myeloma treatment with osteoanabolic therapy (i.e. any treatment that induces increased osteoblastic number or activity) are enumerated. Our goal is to illuminate novel mechanisms by which osteoblasts may contribute to multiple myeloma disease progression and osteolysis to better direct research efforts. Ultimately, we hope this may provide a roadmap for new approaches to the pathogenesis and treatment of multiple myeloma with a particular focus on the osteoblast.

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Relationship between abnormal osteoblasts and cellular immunity in multiple myeloma

Cited by 9 publications

References 19 publications

Osteoblast inhibition by chemokine cytokine ligand3 in myeloma-induced bone disease

Osteoblast inhibition by chemokine cytokine ligand3 in myeloma-induced bone disease

Abnormal changes in the quantity and function of osteoblasts cultured in�vitro in patients with myelodysplastic syndrome

Dynamic interplay between bone and multiple myeloma: Emerging roles of the osteoblast

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