Aberrant activation of Wnt signaling pathway altered osteocyte mineralization

Zhou, Yinghong; Lin, Jinying; Shao, Jian Yong; Zuo, Qiliang; Wang, Shengfang; Wolff, Annalena; Nguyen, Dung; Rintoul, Llew; Du, Zhibin; Gu, YuanTong; Peng, Yong; Ramshaw, John A. M.; Long, Xing; Xiao, Yin

doi:10.1016/j.bone.2019.06.027

Cited by 26 publications

(20 citation statements)

References 44 publications

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“…Importance of Wnt signalling in RA pathogenesis was initially evidenced by observing the high expression of Wnt protein and its receptor, frizzled (Fz) complex, in the synovial joint region of patients with RA 54 . Further studies in recent years have shown that Wnt signalling through β‐catenin activation contributes to pleomorphic changes in osteocytes/chondrocytes leading to bone erosion and cartilage degradation in RA 55‐57 . Wnt signalling promotes this effect through the interaction of circulating soluble Wnt proteins with Fz receptor complex majorly expressed on the surface of RAFLS cells.…”

Section: Berberine; a Potential Adjuvant For Ra Managementmentioning

confidence: 99%

Immunomodulatory effects of berberine on the inflamed joint reveal new therapeutic targets for rheumatoid arthritis management

Shen

Jiao

et al. 2020

J Cellular Molecular Medi

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Section: Berberine; a Potential Adjuvant For Ra Managementmentioning

confidence: 99%

Immunomodulatory effects of berberine on the inflamed joint reveal new therapeutic targets for rheumatoid arthritis management

Shen

Jiao

et al. 2020

J Cellular Molecular Medi

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“…Indeed, about 10% of the adult human skeleton is renewed each year and is dependent on the balance between osteoblasts and osteoclasts [ 5 , 8 , 9 , 21 ]. However, as humans age, the balance shifts toward bone resorption, and may lead to bone disorders such as osteopenia and osteoporosis (OP) [ 21 , 22 , 23 , 24 , 25 , 26 ]. Thus, elucidating the precise mechanisms that are responsible for this shift in homeostasis is of the utmost importance.…”

Section: Introductionmentioning

confidence: 99%

Differentiation of Cells Isolated from Human Femoral Heads into Functional Osteoclasts

Halloran

Heubel

MacMurray

et al. 2022

JDB

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Proper formation of the skeleton during development is crucial for the mobility of humans and the maintenance of essential organs. The production of bone is regulated by osteoblasts and osteoclasts. An imbalance of these cells can lead to a decrease in bone mineral density, which leads to fractures. While many studies are emerging to understand the role of osteoblasts, less studies are present about the role of osteoclasts. This present study utilized bone marrow cells isolated directly from the bone marrow of femoral heads obtained from osteoarthritic (OA) patients after undergoing hip replacement surgery. Here, we used tartrate resistant acid phosphatase (TRAP) staining, Cathepsin K, and nuclei to identity osteoclasts and their functionality after stimulation with macrophage-colony stimulation factor (M-CSF) and receptor activator of nuclear factor kappa-β ligand (RANKL). Our data demonstrated that isolated cells can be differentiated into functional osteoclasts, as indicated by the 92% and 83% of cells that stained positive for TRAP and Cathepsin K, respectively. Furthermore, isolated cells remain viable and terminally differentiate into osteoclasts when stimulated with RANKL. These data demonstrate that cells isolated from human femoral heads can be differentiated into osteoclasts to study bone disorders during development and adulthood.

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“…These results indicate that the BMP-2-QDot ® s conjugation can be used to observe BMP-2’s activity, allowing future studies to determine aberrant BMP-2 signaling in diseases such as osteoporosis and osteosarcoma. In addition, although studies measure phosphorylation of Smads to determine BMP-2 activity, here, we use the von Kossa assay to measure bone mineralization as the readout of BMP-2 signaling, as multiple other pathways may be involved, such as fibroblast growth factor (FGF) and Wnt signaling [ 62 , 63 ]. The von Kossa assay measures calcium produced after osteogenesis and as demonstrated by equal cell counts in each condition and the colocalization of BMP-2-QDot ® s and BMPRIa, we confirm that our conjugate is indeed functional ( Figure 4 and Figure 5 ).…”

Section: Discussionmentioning

confidence: 99%

Bone Morphogenetic Protein-2 Conjugated to Quantum Dot®s is Biologically Functional

et al. 2020

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Quantum Dot®s (QDot®s) are novel, semi-conductive nanostructures that emit a certain fluorescence when excited by specific wavelengths. QDot®s are more photostable, brighter, and photobleach less than other fluorescent dyes. These characteristics give them the potential to be used in many biological applications. The shells of QDot®s are coated with functional groups, such as carboxylate and organic groups, allowing them to couple to peptides/proteins and be used for real-time imaging and high-resolution microscopy. Here, we utilize Quantum Dot®s and Bone Morphogenetic Protein-2 (BMP-2) to create a BMP-2-QDot®s conjugate. BMP-2 is a growth factor that drives many processes such as cardiogenesis, neural growth, and osteogenesis. Despite its numerous roles, the trafficking and uptake of BMP-2 into cells is not well-established, especially during progression of diseases. The results presented here demonstrate for the first time a fluorescent BMP-2 analog that binds to the BMP-receptors (BMPRs), remains biologically active, and is stable for long time periods. Previous attempts to develop a biological BMP-2 analog with Fluorescein isothiocyanate (FITC) or nanodiamonds lacked data on the analog’s stability. Furthermore, these analogs did not address whether they can signal within the cell by binding to the BMPRs or were mediated by non-stable conjugates.

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Aberrant activation of Wnt signaling pathway altered osteocyte mineralization

Cited by 26 publications

References 44 publications

Immunomodulatory effects of berberine on the inflamed joint reveal new therapeutic targets for rheumatoid arthritis management

Immunomodulatory effects of berberine on the inflamed joint reveal new therapeutic targets for rheumatoid arthritis management

Differentiation of Cells Isolated from Human Femoral Heads into Functional Osteoclasts

Bone Morphogenetic Protein-2 Conjugated to Quantum Dot®s is Biologically Functional

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