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SummaryBone metabolism is tightly regulated by the immune system. Accelerated bone destruction is observed in many bone diseases, such as rheumatoid arthritis, fracture, and particle-induced osteolysis. These pathological conditions are associated with inflammatory responses, suggesting the contribution of inflammation to bone destruction. Macrophages are heterogeneous immune cells and are polarized into the proinflammatory M1 and antiinflammatory M2 phenotypes in different microenvironments. The cytokines produced by macrophages depend on the macrophage activation and polarization. Macrophages and macrophage-derived cytokines are important to bone loss in inflammatory bone disease. Recent studies have shown that macrophages can be detected in bone tissue and interact with bone cells. The interplay between macrophages and bone cells is critical to bone formation and repair. In this article, we focus on the role of macrophages in inflammatory bone diseases, as well as discuss the latest studies about macrophages and bone formation, which will provide new insights into the therapeutic strategy for bone disease.

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Eleven new unusual C25 steroid isomers with bicyclo[4.4.1]A/B rings, 24- epi-cyclocitrinol (1), 20-O-methyl-24-epi-cyclocitrinol (3), 20-O-methylcyclocitrinol (4), 24-oxocyclocitrinol (7), 12 R-hydroxycyclocitrinol (8), neocyclocitrinols B (10) and D (12), erythro-23-O-methylneocyclocitrinol (13), threo-23-O-methylneocyclocitrinol (14), isocyclocitrinol B (15), and precyclocitrinol B (18), and five known steroids, cyclocitrinol (2), neocyclocitrinols A (9) and C (11), isocyclocitrinol A (16), and 22-O-acetylisocyclocitrinol A (17), were characterized from cultures of the volcanic ash-derived fungus Penicillium citrinum HGY1-5. Their structures and absolute configurations were established by spectroscopic and chemical methods together with X-ray diffraction analysis. Compounds 3, 4, and 10- 14 were determined to be artifacts on the basis of acidic transformation of 1- 4. The biosynthetic origin of these steroids derived from ergosterol was investigated by feeding (13)C-labeled acetates to the growing cultures of P. citrinum HGY1-5. The biological activities of all 16 steroids were tested using the cAMP assay on GPR12-CHO and WT-CHO cells. The results showed that compounds 1, 2, 10, 11, and 14 could induce the production of cAMP in GPR12-transfected CHO cells.

Recent studies suggest that cell therapy may be an effective way to repair intervertebral disc degeneration. As a strong immune suppressor, TGF-β1 has been shown to inhibit inflammation respond effectively. The objective of this study was to explore the effects of TGF-β1 during bone marrow mesenchymal stem cells-based therapy for disc degeneration. In vitro assays demonstrated that co-culturing of nucleus pulposus cells with bone marrow mesenchymal stem cells resulted in significantly higher levels of TGF-βl secretion. This increase inhibited IκB phosphorylation and NF-κB activation, detected by western blot analysis. Meanwhile, in a rabbit model, MRI analysis revealed significant recovery of signal intensity in the degenerative discs of rabbits receiving cells transplantation, than receiving cells treated with a TGF-β1 inhibitor or saline. These findings indicated that enhanced TGF-β1 production recovered the degeneration of intervertebral disc. And also immunohistochemical staining detected enhanced collagen II expression in the rabbits treated with cell transplantation. However, the NF-κB positive cells were significantly less than other two control groups. Thus, cell therapy promoted TGF-β1 expression in nucleus pulposus, leading to anti-inflammatory effects via the inhibition of NF-κB, and the amelioration of disc degradation due to increased expression of collagen II and aggrecan in degenerative intervertebral disc.