A Novel Role of Interleukin-6 as a Regulatory Factor of Inflammation-Associated Deterioration in Osteoblast Arrangement

Abstract

Inflammatory disorders are associated with bone destruction; that is, deterioration in bone cell activities are under the control of the innate immune system. Macrophages play a central role in innate immunity by switching their polarized phenotype. A disturbed immune system causes aberrance in the ordered bone matrix microarrangement, which is a dominant determinant of bone tissue functionalization. However, the precise relationship between the immune system and bone tissue organization is unknown. In this study, the controlled in vitro co-culture assay results showed that M1-polarized macrophages disrupted the osteoblast alignment, which directly modulate the oriented bone matrix organization, by secreting pro-inflammatory cytokines. Notably, interleukin-6 was found to be a key regulator of unidirectional osteoblast alignment. Our results demonstrated that inflammatory diseases triggered bone dysfunction by regulating the molecular interaction between the immune system and bone tissue organization. These findings may contribute to the development of therapeutic targets for inflammatory disorders, including rheumatoid arthritis.

Inflammasomes in Alveolar Bone Loss

“…When inflammasomes are activated, osteoblasts promote osteoclastogenesis via increased production of cytokines and chemokines, such as RANKL and CX3CL1, or decreased OPG levels, as described above ( 107 ). IL-1β also affects osteoblast arrangement ( 143 ). However, production of IL-1β and IL-18 proteins in bacteria-infected osteoblasts remains controversial ( 144 , 145 ).…”

Superior Alignment of Human iPSC-Osteoblasts Associated with Focal Adhesion Formation Stimulated by Oriented Collagen Scaffold

“…Several bone disorders in humans have limited treatment possibilities because of the inaccessibility of the affected bones. Genetic disorders, such as osteopetrosis [45] and osteogenesis imperfecta [46]; acquired disorders, including osteoporosis [47,48], cancer bone metastasis [49,50], and chronic kidney disease (CKD) [51]; regenerated bone [13,52]; and drug treatment [53,54] affect bone matrix microstructures, demonstrating the involvement of various biological mechanisms, including the autonomous or mutual activity of bone cells and their related biomolecules, in the formation of bone microstructure [55]. The biological mechanism underlying changes in the bone microstructure upon the emergence of bone disorders may be revealed in the future by an iPSC-based disease model composed of patient-derived hiPSC-Obs and the culture platform introduced in this study.…”

Lactoferrin-Anchored Tannylated Mesoporous Silica Nanomaterials for Enhanced Osteo-Differentiation Ability

“…Osteo-differentiation is divided into three steps: proliferation, matrix formation, and mineralization [ 47 ]. Alkaline phosphatase, a well-known cell membrane-associated enzyme, has previously shown early expression coincident with osteoblast differentiation and has been widely suggested to be an early osteoblastic differentiation marker [ 28 , 29 , 47 , 48 ]. In addition, increased ALP level has been shown to be associated with matrix formation in osteoblasts, prior to onset of mineralization [ 49 ].…”

“…OCN and OPN , which are known to regulate osteoblast differentiation, show increased expression in osteoblast-like cells [ 28 , 29 ]. OCN , an element expressed and secreted only by osteoblasts, has been used as a serum marker of bone formation [ 48 , 50 ]. OPN , a versatile extracellular matrix-related glycoprotein, is important in parathyroid hormone (PTH) regulation [ 51 ].…”