Roles of Altered Macrophages and Cytokines: Implications for Pathological Mechanisms of Postmenopausal Osteoporosis, Rheumatoid Arthritis, and Alzheimer’s Disease

Abstract

Postmenopausal osteoporosis (PMOP) is characterized by the uncoupling of bone resorption and bone formation induced by estrogen deficiency, which is a complex outcome related to estrogen and the immune system. The interaction between bone and immune cells is regarded as the context of PMOP. Macrophages act differently on bone cells, depending on their polarization profile and secreted paracrine factors, which may have implications for the development of PMOP. PMOP, rheumatoid arthritis (RA), and Alzheimer’s disease (AD) might have pathophysiological links, and the similarity of their pathological mechanisms is partially visible in altered macrophages and cytokines in the immune system. This review focuses on exploring the pathological mechanisms of PMOP, RA, and AD through the roles of altered macrophages and cytokines secretion. First, the multiple effects on cytokines secretion by bone-bone marrow (BM) macrophages in the pathological mechanism of PMOP are reviewed. Then, based on the thought of “different tissue-same cell type-common pathological molecules-disease pathological links-drug targets” and the methodologies of “molecular network” in bioinformatics, highlight that multiple cytokines overlap in the pathological molecules associated with PMOP vs. RA and PMOP vs. AD, and propose that these overlaps may lead to a pathological synergy in PMOP, RA, and AD. It provides a novel strategy for understanding the pathogenesis of PMOP and potential drug targets for the treatment of PMOP.

Macrophages and Bone Remodeling

“…(5)(6)(7) Increasing evidence shows that other myeloid cells influence osteoclasts and osteoblasts to modulate bone remodeling and support skeletal homeostasis. (7,8) Consistent with this notion, coding variations and genetic mutations to macrophage phenotypic genes can result in altered bone mass in humans (Table 1). In this review, we discuss pertinent literature supporting roles for macrophages in governing bone remodeling.…”

The immunosuppressive effects and mechanisms of loureirin B on collagen-induced arthritis in rats

“…Antigen-activated T cells selectively enter specific parts of the joint with the interaction of chemokine (CK) and its receptors, homing receptors, and addressins, causing slippage ( 26 ). Inflammatory infiltration of membranous tissue leads to exacerbation of the disease.…”

“…Inflammatory infiltration of membranous tissue leads to exacerbation of the disease. Distributed T cells in lymphoid organs and lymphoid tissues generate immune responses to antigens carried by the blood and lymphatic circulation ( 26 ). The immune response produces pro-inflammatory cytokines that further exacerbate inflammatory infiltration and cartilage damage at diseased sites in RA patients.…”

“…The cytokines IL-1β, IL-2, IL-4, IL-6, IL-10 and IL-17 are involved in the development of RA ( 26 , 27 ). Studies have found that the levels of cytokines in the serum of RA patients are significantly increased, and their levels are positively correlated with severity of the disease in RA patients ( 27 ).…”

Mechanisms by which kidney-tonifying Chinese herbs inhibit osteoclastogenesis: Emphasis on immune cells

“… Yao et al (2021) The M1phenotype is an inflammatory that is activated by cytokines, and its related cytokines can promote OC formation and bone resorption, while the M2 phenotype is a repair in which related cytokines, such as IL-4 and IL-10, can inhibit OC function and promote osteogenesis. Xu et al (2022) ; Yang and Wan (2019) ( Figure 1 ).…”