Curcumin Modulates the Crosstalk Between Macrophages and Bone Mesenchymal Stem Cells to Ameliorate Osteogenesis

Abstract

Bone healing is thought to be influenced by the cross-talk between bone forming and immune cells. In particular, macrophages play a crucial role in the regulation of osteogenesis. Curcumin, the major bioactive polyphenolic ingredient of turmeric, has been shown to regulate inflammatory response and osteogenic activities. However, whether curcumin could regulate macrophage polarization and subsequently influence osteogenesis remain to be elucidated. In this study, the potential immunomodulatory capability of curcumin on inflammatory response and phenotype switch of macrophages and the subsequent impact on osteogenic differentiation of MSCs are investigated. We demonstrated that curcumin exhibited significant anti-inflammatory effect by polarizing the macrophages toward anti-inflammatory phenotype, with increased expression of IL-4, IL-10, and CD206, and decreased expression of IL-1β, TNF-α, CCR7, and iNOS. In addition, curcumin could improve the osteo-immune microenvironment via promoting osteogenesis-related regenerative cytokine BMP-2 and TGF-β production. Moreover, the co-cultured test of macrophages and BMSCs showed that curcumin-modulated macrophages conditioned medium could promote osteogenic differentiation of BMSCs with increased gene (ALP, Runx-2, OCN, and OPN) and protein (Runx-2 and OCN) expression levels, enhanced ALP activity, and obvious formation of mineralized nodules. Taken together, with the interaction between curcumin-conditioned macrophage and curcumin-stimulated BMSCs, curcumin could remarkably enhance the osteogenic differentiation of BMSCs in LPS-activated inflammatory macrophage-BMSCs coculture system.

Sequential gastrodin release PU/n-HA composite scaffolds reprogram macrophages for improved osteogenesis and angiogenesis

“…To this end, the tailorable cues of biomaterials regarding surface topography, hydrophilicity, porosity, and materials dynamics and mechanics [ [35] , [36] , [37] ] can be considered for modulating the macrophage immune response. The main bioactive constituents of the traditional Chinese herbal medicines (e.g., Icariin [ 38 ], curcumin [ 39 ]) have also been applied to immunomodulation because of their anti-inflammatory properties and bone healing-enhancing effects. However, due to their complex chemical structure, the constituents are rarely used as a chemical synthesis component of biomaterials.…”

Long‐Term Recruitment of Endogenous M2 Macrophages by Platelet Lysate‐Rich Plasma Macroporous Hydrogel Scaffold for Articular Cartilage Defect Repair

“…[7,8] Recent studies have illustrated that inducing anti-inflammatory macrophage (M2) polarization from M1 macrophage via biomaterials could suppress inflammatory immune cells and promote cartilage tissue regeneration by producing antiinflammatory factors, such as transforming growth factor-beta (TGF-𝛽) and interleukin-10 (IL-10). [9][10][11][12] For instance, Dai et al reported a double-network hydrogel based on squid cartilage type II gelatin and hyaluronic acid, which could control the M1/M2 phenotype switch and then stimulate the chondrogenesis of cartilage stem/progenitor cells through the M2 macrophage-mediated TGF-𝛽/Smad pathway. [13] Zhai et al demonstrated that a ceramic lithium calcium silicate scaffold promoted cartilage repair by upregulating the expression of IL-10 and suppressing the expression of inflammatory genes.…”

Lipopolysaccharide-activated macrophages regulate the osteogenic differentiation of bone marrow mesenchymal stem cells through exosomes

“…Macrophage paracrine signalling is an important pathway that regulates BMSC osteogenic differentiation. The uptake of paracrine vesicles, exosomes, and other cytokines by BMSCs can upregulate the transcription levels of alkaline phosphatase (ALP), Runt-related transcription factor 2 (RUNX2), osteocalcin, and osteopontin and the protein expression levels of RUNX2 and osteocalcin, enhancing the activity of ALP ( Chen et al, 2021 ). Additionally, lipopolysaccharide-activated macrophages can promote the migration of BMSCs through paracrine IL-6 and inducible nitric oxide synthase ( Lei et al, 2021 ).…”