Low-Dose Staphylococcal Enterotoxin C2 Mutant Maintains Bone Homeostasis via Regulating Crosstalk between Bone Formation and Host T-Cell Effector Immunity.

Studies in recent years have highlighted an elaborate crosstalk between T cells and bone cells, suggesting that T cells may be alternative therapeutic targets for the maintenance of bone homeostasis. Here, it is reported that systemic administration of low-dose staphylococcal enterotoxin C2 (SEC2) 2M-118, a form of mutant superantigen, dramatically alleviates ovariectomy (OVX)-induced bone loss via modulating T cells. Specially, SEC2 2M-118 treatment increases trabecular bone mass significantly via promoting bone formation in OVX mice. These beneficial effects are largely diminished in T-cell-deficient nude mice and can be rescued by T-cell reconstruction. Neutralizing assays determine interferon gamma (IFN-γ) as the key factor that mediates the beneficial effects of SEC2 2M-118 on bone. Mechanistic studies demonstrate that IFN-γ stimulates Janus kinase/signal transducer and activator of transcription (JAK-STAT) signaling, leading to enhanced production of nitric oxide, which further activates p38 mitogen-activated protein kinase (MAPK) and Runt-related transcription factor 2 (Runx2) signaling and promotes osteogenic differentiation. IFN-γ also directly inhibits osteoclast differentiation, but this effect is counteracted by proabsorptive factors tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1ß) secreted from IFN-γ-stimulated macrophages. Taken together, this work provides clues for developing innovative approaches which target T cells for the prevention and treatment of osteoporosis.

Chemical constituents of Cynanchum wilfordii and the chemotaxonomy of two species of the family Asclepiadacease, C. wilfordii and C. auriculatum.

Definitive identification of original plant species is important for standardizing herbal medicine. Although only the dried roots of Cynanchum wilfordii (Asclepiadaceae) are prescribed as Cynanchi Wilfordii Radix in Korean Pharmacopoeia, the roots of C. wilfordii and C. auriculatum are often misused in the Korean herbal market due to their morphological similarity and similar name. Therefore, it would be very useful to discover an effective chemical marker for the identification of the two species. To this end, we carried out a phytochemical study on the roots of C. wilfordii. As a result, twenty compounds were isolated from the roots of C. wilfordii and their chemical structures were identified as ß-sitosterol (1), wilfoside C1N (2), wilfoside C3N (3), wilfoside K1N (4), methyleugenol (5), wilfoside C1G (6), cynauriculoside A (7), daucosterol (8), 2,4-dihydroxyacetophenone (9), cynandione A (10), 2,5-dihydroxyacetophenone (11), acetovanillone (12), p-hydroxyacetophenone (13), sucrose (14), conduritol F (15), geniposide (16), succinic acid (17), 3-(ß-D-ribofuranosyl)-2,3-dihydro-6H-1,3-oxazine-2,6-dione (18), bungeiside A (19), cynanoneside B (20). Among them, compounds 15, 16, 18, 19, and 20 were isolated for the first time from this species. Furthermore, conduritol F (15) was demonstrated to be contained only in C. wilfordii. Therefore, it may be useful as a chemical marker to identify the two species C. wilfordii and C. auriculatum.