Bone fracture healing is a complex, dynamic process that involves various cell types, with osteoclasts and osteoblasts playing indispensable roles. In this study, we found that psoralen, the main active ingredient in Psoralea corylifolia L. fruit extract, enhanced bone fracture healing through activation of osteoclast and osteoblast activity via the ERK signaling pathway. In detail, psoralen promoted receptor activator of nuclear factor‐κB ligand‐induced osteoclastogenesis, mRNA expression of osteoclast‐specific genes, and osteoclastic bone resorption in primary bone marrow‐derived macrophages. Meanwhile, psoralen induced osteogenic differentiation by promoting the mRNA expression of the osteoblast differentiation markers alkaline phosphatase, runt‐related transcription factor 2, osterix, and osteocalcin. At the molecular level, psoralen preferentially activated ERK1/2 but not JNK or p38 MAPKs. Further experiments revealed that psoralen‐induced osteoclast and osteoblast differentiation was abrogated by a specific inhibitor of phosphorylated ERK. In addition, psoralen accelerated bone fracture healing in a rat tibial fracture model, and the numbers of osteoclasts and osteoblasts were increased in psoralen‐treated fracture callus. Taken together, our findings indicate that psoralen accelerates bone fracture healing through activation of osteoclasts and osteoblasts via ERK signaling and has potential as a novel drug in the orthopedic clinic for the treatment of bone fractures.—Zhang, T., Han, W., Zhao, K., Yang, W., Lu, X., Jia, Y., Qin, A., Qian, Y. Psoralen accelerates bone fracture healing by activating both osteoclasts and osteoblasts. FASEB J. 33, 5399–5410 (2019). http://www.fasebj.org

Osteoporosis is an osteolytic disorder commonly associated with excessive osteoclast formation. Transcriptional coactivator with PDZ-binding motif (TAZ) is a key downstream effector of the Hippo signaling pathway; it was suggested to be involved in the regulation of bone homeostasis. However, the exact role of TAZ in osteoclasts has not yet been established. In this study, we demonstrated that global knockout and osteoclast-specific knockout of TAZ led to a low-bone mass phenotype due to elevated osteoclast formation, which was further evidenced by in vitro osteoclast formation assays. Moreover, the overexpression of TAZ inhibited RANKL-induced osteoclast formation, whereas silencing of TAZ reduced it. Mechanistically, TAZ bound to TGF-activated kinase 1 (TAK1) and reciprocally inhibited NF-κB signaling, suppressing osteoclast differentiation. Collectively, our findings highlight an essential role of TAZ in the regulation of osteoclastogenesis in osteoporosis and its underlying mechanism.

The Jinshan gold deposit is located in the Neoproterozoic Jiangnan orogen between the Yangtze and Cathaysia blocks. Gold‐bearing disseminated ores are associated with the earlier stage of NWW‐trending ductile zone, and auriferous quartz vein‐type ores show an intimate relationship with the later stage of NE‐trending brittle‐ductile zones. Fluid‐inclusion studies were conducted on the quartz veins. Three types of fluid inclusions can be identified: H2O–CO2 inclusions (type I), CO2‐rich inclusions (type II), and aqueous inclusions (type III). The pre‐ore stage, quartz‐pyrite veins primarily contain type I inclusions with constant CO2 bubble volumetric proportions. The main gold mineralization‐stage veins have all three types of inclusions with variable gas‐phase ratios and CO2 contents. The post‐ore stage carbonate±chlorite veinlets only contain type III inclusions. Type I inclusions in the pre‐ore stage display homogenization temperatures (Th) of 285–340°C, with salinities of 1.4–6.1 wt.% NaCl equivalent. In the main gold mineralization stage, type II and III inclusions show similar Th at 208–277°C, but contrasting salinity values with 0.6–3.6 and 3.5–8.9 wt.% NaCl equivalent, and type I inclusions show variable CO2‐phase proportions and have Th of 241–292°C and salinities of 1.0–7.0 wt.% NaCl equivalent. In the post‐ore stage, type III inclusions yield Th of 109–201°C and salinities of 1.1–6.4 wt.% NaCl equivalent. Petrological observations and microthermometric results show that fluid immiscibility primarily occurred during the gold mineralization stages. The oxygen and hydrogen isotope compositions (δ18 O = +6.9‰ to +11.2‰, δD = −71‰ to −46‰) of inclusion water in quartz grains imply that ore fluids were principally metamorphic in origin. The sulfur and lead values of sulfide from the ores are analogous to those from the basement strata, suggesting a predominantly crustal source of the ore sulfides. The Jinshan deposit is a typical orogenic gold deposit.

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