Bone regeneration in inflammation with aging and cell-based immunomodulatory therapy

作者：Junichi Kushioka, Simon Kwoon‐Ho Chow, Masakazu Toya, Masanori Tsubosaka, Huaishuang Shen, Qi Gao, Xueping Li, Ning Zhang, Stuart B. Goodman · 发表于：Inflammation and Regeneration · 年份：2023 · DOI：10.1186/s41232-023-00279-1 · 被引用次数：158 · 研究领域：Mesenchymal stem cell research、Osteoarthritis Treatment and Mechanisms、Periodontal Regeneration and Treatments

Aging of the global population increases the incidence of osteoporosis and associated fragility fractures, significantly impacting patient quality of life and healthcare costs. The acute inflammatory reaction is essential to initiate healing after injury. However, aging is associated with "inflammaging", referring to the presence of systemic low-level chronic inflammation. Chronic inflammation impairs the initiation of bone regeneration in elderly patients. This review examines current knowledge of the bone regeneration process and potential immunomodulatory therapies to facilitate bone healing in inflammaging.Aged macrophages show increased sensitivity and responsiveness to inflammatory signals. While M1 macrophages are activated during the acute inflammatory response, proper resolution of the inflammatory phase involves repolarizing pro-inflammatory M1 macrophages to an anti-inflammatory M2 phenotype associated with tissue regeneration. In aging, persistent chronic inflammation resulting from the failure of M1 to M2 repolarization leads to increased osteoclast activation and decreased osteoblast formation, thus increasing bone resorption and decreasing bone formation during healing.Inflammaging can impair the ability of stem cells to support bone regeneration and contributes to the decline in bone mass and strength that occurs with aging. Therefore, modulating inflammaging is a promising approach for improving bone health in the aging population. Mesenchymal stem cells (MSC...