Osteoimmunology: Influence of the Immune System on Bone Regeneration and Consumption

Abstract

Stimulating bone regeneration is a central aim in orthopaedic and trauma surgery. Although the replacement of bone with artificial materials like cement or apatite helps to keep up bone stability, new bone often cannot be regenerated. Increasing research efforts have led to the clinical application of growth factors stimulating bone growth (e.g. bone morphogenic protein, BMP) and inhibitors preventing bone consumption (e.g. RANKL blocking antibodies). These factors mostly concentrate on stimulating osteoblast or preventing osteoclast activity. It is widely accepted that osteoblasts and osteoclasts are central players in bone regeneration. This concept assumes that osteoblasts are responsible for bone growth while osteoclasts cause bone consumption by secreting matrix-degrading enzymes such as cathepsin K and matrix metalloproteinases (MMP). However, according to new research results, bone growth or consumption are not regulated by single cell types. It is rather the interaction of various cell types that regulates bone metabolism. While factors secreted by osteoblasts are essential for osteoclast differentiation and activation, factors secreted by activated osteoclasts are essential for osteoblast activity. In addition, recent research results imply that the influence of the immune system on bone metabolism has long been neglected. Factors secreted by macrophages or T cells strongly influence bone growth or degradation, depending on the bone microenvironment. Infections, sterile inflammation or tumour metastases not only affect bone cells directly, but also influence immune cells such as T cells indirectly. Furthermore, immune cells and bone are mechanistically regulated by similar factors such as cytokines, chemokines and transcription factors, suggesting that the definition of bone and immune cells has to be thought over. Bone and the immune system are regulated by similar mechanisms. These newly identified similarities between bone and the immune system imply that medication developed for tumour and autoimmune patients could also be applied in bone diseases.

The Effects of Biomaterial Implant Wear Debris on Osteoblasts

“…Although it is known that the chronic inflammatory reaction that occurs in response to biomaterial wear debris is mostly driven by macrophages, osteolysis is also indirectly caused by a partial contribution of several cell types such as osteoblasts, dendritic cells, osteoclasts, and synovial fibroblasts (Limmer and Wirtz, 2017;Li et al, 2018). Upon wear particle challenge, macrophages release an array of proinflammatory mediators, which trigger the recruitment, multiplication, differentiation, and maturation of osteoclast precursors.…”

The predictive role of monocyte-to-lymphocyte ratio in osteoporosis patient

“…“Bone immunology” views the immune system and immune factors as important roles in the development of osteoporosis. [11,12] Research has not previously confirmed the correlation between MLR with osteoporosis. In this study, we evaluated the diagnostic value of MLR in osteoporosis.…”

Prevention and Treatment of Osteoporosis Using Chinese Medicinal Plants: Special Emphasis on Mechanisms of Immune Modulation

“…The primary pathological process of osteoporosis is the imbalance of bone resorption and bone formation during bone remodeling. T cells regulate bone cells and hematopoiesis in the immune system, and these cells secrete inflammatory factors and Wnt ligands to promote bone formation and absorption [ 2 , 3 , 36 ]. T cells also regulate the dynamic balance of metabolism between bone mesenchymal cells and osteoblasts via CD40 ligands and costimulatory molecules [ 37 ].…”

“…The etiology of osteoporosis is primarily concentrated in endocrine and metabolic disorders. However, osteoimmunology demonstrated that the immune system and immune factors may be involved in the development of osteoporosis and play important regulatory roles [ 2 , 3 ]. The microenvironment created by bone cells provides conditions for development of the immune system, which regulates bone metabolism via B cells, T cells, dendritic cells, and many cytokines [ 2 – 5 ].…”

“…However, osteoimmunology demonstrated that the immune system and immune factors may be involved in the development of osteoporosis and play important regulatory roles [ 2 , 3 ]. The microenvironment created by bone cells provides conditions for development of the immune system, which regulates bone metabolism via B cells, T cells, dendritic cells, and many cytokines [ 2 – 5 ]. Abnormal activation of the immune system alters the balance between osteoblasts and osteoclasts, which results in an imbalance in bone remodeling and causes osteoporosis [ 6 – 8 ].…”