Targeting macrophage polarization as a promising therapeutic strategy for the treatment of osteoarthritis
Weiyun Wang1, Yaru Chu1, Pengyuan Zhang2
1The Third Affiliated Hospital of Xinxiang Medical University, Institutes of Health Central Plain, Clinical Medical Center of Tissue Engineering and Regeneration, Xinxiang Medical University, Xinxiang, China.
Abstract:
Osteoarthritis (OA) is a chronic osteoarthropathy characterized by the progressive degeneration of articular cartilage and synovial inflammation. Early OA clinical treatments involve intra-articular injection of glucocorticoids, oral acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs), which are used for anti-inflammation and pain relief. However, long-term use of these agents will lead to inevitable side effects, even aggravate cartilage loss. At present, there are no disease-modifying OA drugs (DMOADs) yet approved by regulatory agencies. Polarization regulation of synovial macrophages is a new target for OA treatment. Inhibiting M1 polarization and promoting M2 polarization of synovial macrophages can alleviate synovial inflammation, relieve joint pain and inhibit articular cartilage degradation, which is a promising strategy for OA treatment. In this study, we describe the molecular mechanisms of macrophage polarization and its key role in the development of OA. Subsequently, we summarize the latest progress of strategies for OA treatment through macrophage reprogramming, including small molecule compounds (conventional western medicine and synthetic compounds, monomer compounds of traditional Chinese medicine), biomacromolecules, metal/metal oxides, cells, and cell derivatives, and interprets the molecular mechanisms, hoping to provide some information for DMOADs development.
Insights
Targeting macrophage polarization offers a novel approach to osteoarthritis (OA) treatment by reducing inflammation and cartilage damage. This strategy aims to develop disease-modifying OA drugs (DMOADs) to overcome limitations of current therapies.
Area of Science:
- Immunology
- Orthopedics
- Pharmacology
Background:
- Osteoarthritis (OA) involves cartilage degeneration and synovial inflammation, with current treatments offering limited relief and potential side effects.
- Existing OA therapies lack disease-modifying capabilities, highlighting the need for novel therapeutic strategies.
- Macrophage polarization in the synovium is increasingly recognized as a critical factor in OA pathogenesis.
Purpose of the Study:
- To elucidate the molecular mechanisms of macrophage polarization in OA development.
- To review current therapeutic strategies targeting macrophage reprogramming for OA treatment.
- To provide insights for the development of new disease-modifying osteoarthritis drugs (DMOADs).
Main Methods:
- Review of molecular mechanisms underlying macrophage polarization in osteoarthritis.
- Summary of recent advancements in OA treatment strategies focusing on macrophage reprogramming.
- Analysis of various therapeutic modalities including small molecules, biomacromolecules, metals, and cell-based therapies.
Main Results:
- Macrophage polarization, specifically M1 inhibition and M2 promotion, effectively alleviates synovial inflammation, joint pain, and cartilage degradation in OA.
- Diverse therapeutic approaches, including traditional medicines and advanced biomaterials, show promise in modulating macrophage polarization.
- Understanding these mechanisms is crucial for developing effective DMOADs.
Conclusions:
- Modulating synovial macrophage polarization presents a promising therapeutic avenue for osteoarthritis.
- Reprogramming macrophages offers a potential strategy to develop the first generation of DMOADs.
- Further research into macrophage polarization mechanisms can accelerate the development of novel OA treatments.
