Fig. 8
(Schematic figure created with BioRender.com)
Inflammatory M1 macrophage negatively affects osteocyte maturation and mineralization via inhibiting Notch signaling pathway. Osteocyte maturation requires activation of the Notch signaling pathway. Only mature osteocytes produce DMP1 which is critical in bone mineralization. DMP1 is the transporter of calcium phosphate, only with which minerals and collagen fibers combine regularly to form well crystallized bone structure. Inflammatory M1 macrophages inhibit Notch signaling pathway in osteocytes, preventing osteocytes reaching maturity. Immature osteocytes cannot produce DMP1. Lack of DMP1 calcium phosphate cannot be transported into collagen gap zones, therefore minerals cannot integrate into collagen fibers in an organized manner and calcium deposition is formed. Disorganized bone mineralization finally forms abnormal bone structure