echemi logo
Product
  • Product
  • Supplier
  • Inquiry
    Home > Active Ingredient News > Immunology News > Bone Res | Multi-unit cooperation such as the Army Medical University!

    Bone Res | Multi-unit cooperation such as the Army Medical University!

    • Last Update: 2021-05-09
    • Source: Internet
    • Author: User
    Search more information of high quality chemicals, good prices and reliable suppliers, visit www.echemi.com
    Editor’s note iNature is China’s largest academic official account.
    It is jointly created by the doctoral team of Tsinghua University, Harvard University, Chinese Academy of Sciences and other units.
    The iNature Talent Official Account is now launched, focusing on talent recruitment, academic progress, scientific research information, interested parties can Long press or scan the QR code below to follow us.

    iNature Ankylosing Spondylitis (AS) is a chronic inflammatory arthritis with progressive fusion of the axial joints.

    Anti-inflammatory therapy (such as anti-TNF-α antibody therapy) can inhibit inflammation, but it cannot effectively prevent the development of spinal fusion in AS patients.

    On January 11, 2021, Cao Xu from Johns Hopkins University, Weng Xisheng from Peking Union Medical College of Chinese Academy of Medical Sciences and Xu Jianzhong from Army Military Medical University jointly published an online publication titled "Chondrogenesis mediates progression of ankylosing spondylitis" in Bone Research (IF=11.
    51) Through heterotopic ossification" research paper, the study reported that the autoimmune inflammation of AS creates a microenvironment that promotes the formation of cartilage of the spinal ligament and becomes a process of spinal fusion.

    Chondrocyte differentiation was observed in the ligaments of patients with early AS, and calcification after cartilage formation.

    In addition, a large number of osteoclasts are found in the inflammatory environment of ligaments and the bone surface of calcified cartilage.

    The resorption activity of these giant osteoclasts produces bone marrow with high levels of active TGF-β, thereby inducing new bone formation in the ligament.

    It is worth noting that no Osterix + osteoprogenitor cells were found in the osteoclast resorption area, indicating that there is no coupling between bone resorption and bone formation.

    Even in the advanced and mature stages, uncoupled osteoclast resorption in the bony interspinous ligament can activate TGF-β, thereby inducing the progression of ossification in AS patients.

    In the progression of AS, the ossification caused by the absorption of calcified cartilage by osteoclasts is a similar pathological process of acquired heterotopic ossification (HO).

    The discovery of cartilage formation in the ligaments of AS patients indicates that the pathogenesis of spinal fusion is the process of HO, and explains why anti-inflammatory treatment does not slow the rate of ankylosing response once new bone formation occurs in the soft tissues of the spinal column.

    Therefore, inhibition of HO formation, such as osteoclast activity, cartilage formation, or TGF-β activity may be a potential therapy for AS.

    In addition, on January 11, 2021, Army Military Medical University Dou Ce, Dong Shiwu and Xu Jianzhong jointly published a research paper entitled "Osteoclast-derived apoptotic bodies couple bone resorption and formation in bone remodeling" in Bone Research (IF=11.
    51) online This study determined the molecular characteristics of ABs derived from osteoclasts at different stages of differentiation and studied their corresponding functions.

    AB was isolated from apoptotic bone marrow macrophages, osteoclasts and mature osteoclasts induced by staurosporine.

    The analysis of proteomics characteristics by liquid chromatography-tandem mass spectrometry showed that there are significant differences in protein load between different ABs.

    Further bioinformatics analysis showed that the proteomic characteristics of AB are highly similar to its parental cells.

    Functionally, pOC-AB induces endothelial progenitor cell differentiation and increases CD31hiEmcnhi endothelial cell formation in a murine bone defect model through its PDGF-BB cargo.

    mOC-ABs induce osteogenic differentiation of mesenchymal stem cells and promote osteogenic differentiation through RANKL reverse signaling.

    In summary, this study has drawn a detailed proteomic map of the osteoclast-derived AB, and shows its potential biological role is crucial to the coupling of bone formation and resorption in the process of bone remodeling (click to read).

    Ankylosing spondylitis (AS) is an autoimmune disease that mainly affects the spine and joints.
    The hardness of soft tissues including ligaments gradually increases.
    It is a common type of spondyloarthritis.

    The prevalence of AS worldwide is estimated to be 0.
    1% to 0.
    32%.

    The disease affects nearly 1.
    3 million to 1.
    6 million patients in Europe, 4.
    6 to 5.
    0 million patients in Asia, and is more common in North America, with a prevalence rate of 31.
    9 per 10,000 population.

    Inflammation usually leads to calcification and bone formation, and has destructive bone lesions, leading to spinal fusion, loss of elasticity, and chronic back pain.

    In the past decade, significant progress has been made in understanding the cause of this autoimmune disease and developing inflammatory treatments.

    Immune cells and innate cytokines, especially human leukocyte antigen (HLA)‑B27 and interleukin 23/17 axis, are crucial in the pathogenesis of AS.

    Since its discovery, HLA-B27 has been considered the main genetic risk factor for AS.

    Advances in research on autoimmune diseases and anti-inflammatory treatments have not slowed the ankylosing response, mainly because of the limited understanding of how inflammation induces axial joint fusion.

    As shown by MRI, anti-TNF-α antibody treatment can effectively reduce 80% of active inflammatory lesions within 6-24 months, and this reduction is also expected to prevent the development of AS.

    Long-term anti-TNFα treatment with different anti-TNF-α agents can improve the spinal inflammation in patients with AS, but no signs have been found to inhibit the progression of structural damage.

    In fact, the occurrence of tonic diseases is not related to inflammation.

    Patients receiving anti-inflammatory treatments still develop cartilage and cellulite at the age of 16.

    MRI did not detect the site of inflammation.

    Acquired heterotopic ossification (HO) is a painful and debilitating disease characterized by the formation of skeletal exoskeleton after injury.

    Transforming growth factor-β (TGF-β) initiates and promotes HO in four stages: (1) inflammation, (2) cartilage formation, (3) osteogenesis, and (4) maturation.

    Chondrocyte differentiation and cartilage formation are the intermediate stages before HO.

    In most cases, HO is obtained, but it can also be detected in some rare genetic diseases, such as progressive bone hyperplasia (FOP) and progressive bone dysplasia.

    It is worth noting that the absorption of calcified cartilage by osteoclasts will activate excessive active TGF-β, thereby recruiting mesenchymal matrix/progenitor cells for ectopic bone formation in the HO microenvironment.

    Even in the mature stage, active TGF-β continues to be absorbed and released by osteoclasts, thereby driving the process of HO.

    In this study, chondrocyte differentiation and cartilage formation in spinal ligaments of patients with early AS were found.

    A large number of huge osteoclasts were observed on the bone surface, and their activity TGF-β increased, thereby promoting the recruitment of Osterix+ osteoprogenitor cells to ossify the spine.

    The results showed that AS progression also went through the same stages: inflammation, cartilage formation, osteogenesis and maturation as the pathogenesis of acquired HO.

    Therefore, inhibition of cartilage formation and osteoclast resorption activity can be an effective treatment for AS.

    Reference message:
    This article is an English version of an article which is originally in the Chinese language on echemi.com and is provided for information purposes only. This website makes no representation or warranty of any kind, either expressed or implied, as to the accuracy, completeness ownership or reliability of the article or any translations thereof. If you have any concerns or complaints relating to the article, please send an email, providing a detailed description of the concern or complaint, to service@echemi.com. A staff member will contact you within 5 working days. Once verified, infringing content will be removed immediately.

    Contact Us

    The source of this page with content of products and services is from Internet, which doesn't represent ECHEMI's opinion. If you have any queries, please write to service@echemi.com. It will be replied within 5 days.

    Moreover, if you find any instances of plagiarism from the page, please send email to service@echemi.com with relevant evidence.