The Inflammatory Contribution of B-Lymphocytes and Neutrophils in Progression to Osteoporosis

Abstract

Osteoporosis is a bone disease characterized by structural deterioration and low bone mass, leading to fractures and significant health complications. In this review, we summarize the mechanisms by which B-lymphocytes and neutrophils contribute to the development of osteoporosis and potential therapeutics targeting these immune mediators to reduce the proinflammatory milieu. B-lymphocytes—typically appreciated for their canonical role in adaptive, humoral immunity—have emerged as critical regulators of bone remodeling. B-lymphocytes communicate with osteoclasts and osteoblasts through various cytokines, including IL-7, RANK, and OPG. In inflammatory conditions, B-lymphocytes promote osteoclast activation and differentiation. However, B-lymphocytes also possess immunomodulatory properties, with regulatory B-lymphocytes (Bregs) secreting TGF-β1 to restrain pathogenic osteoclastogenesis. Neutrophils, the body’s most prevalent leukocyte, also contribute to the proinflammatory environment that leads to osteoporotic bone remodeling. In aged individuals, neutrophils display reduced chemotaxis, phagocytosis, and apoptosis. Understanding the delicate interplay between B-lymphocytes and neutrophils in the context of impaired bone metabolism is crucial for targeted therapies for osteoporosis.

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“…However, further discussion is needed on the two main aspects of the potential relationship between B cells and osteoporosis: an osteoprotective function in physiological conditions and a bone-destructive function in pathological states. In the bone marrow microenvironment, B lymphocytes are unable to mature in the absence of secretory factors from mesenchymal and osteoblastic cells ( 49 ). Bruton’s tyrosine kinase (BTK) is an enzyme integral to signaling in pre-B cell receptors (pre-BCRs) ( 50 ).…”

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“…Patients with advanced inflammatory diseases and malignant tumors often exhibit elevated levels of NLR as a typical manifestation of systemic inflammatory response. This is due to the presence of pro-inflammatory cytokines in their blood, which can cause changes in the tissue microenvironment [ 33 ]. These changes can be used to stratify cancer and are often associated with tumor size, stage, metastatic potential, and lymphatic infiltration.…”

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“…Therefore, the extent to which OPG interferes with the binding between RANKL and RANK determines the rate of bone resorption. Several lymphocytes are involved throughout the production process and pathway regulation ( Song et al, 2020 ; Frase et al, 2023 ). Thus, it can be deemed that the signaling pathway serves as a link between various OBs, immune cells, and cytokines, influencing the formation and differentiation of OBs and OCs.…”

“…Immune cells produce a variety of cytokines that regulate the production and activity of OB and OC through RANKL-dependent or -independent pathways, influencing bone homeostasis. These cytokines include interleukin-8 (IL-8) (Niu et al, 2019), IL-18 (Mansoori et al, 2016), IL-33 (De Martinis et al, 2020a), IL-34 (Xu et al, 2021), IL-37 (Ye et al, 2019), transforming growth factorβ (TGF-β) (Cao et al, 2022) (bone protective factors), IL-1α (Zheng et al, 2021), IL-1β (Otsuka et al, 2023), IL-6 (Wang Several lymphocytes are involved throughout the production process and pathway regulation (Song et al, 2020;Frase et al, 2023). Thus, it can be deemed that the signaling pathway serves as a link between various OBs, immune cells, and cytokines, influencing the formation and differentiation of OBs and OCs.…”