Guodong Li

Osteoarthritis (OA) is characterized by cartilage degradation and subchondral bone remodeling. However, most available studies focus on either cartilage degradation or subchondral bone lesion, alone, and rarely pay attention to the synergy of these two pathological changes. Herein, a dual-functional medication is developed to simultaneously protect cartilage and achieve subchondral bone repair. Black phosphorus nanosheets (BPNSs), with a strong reactive oxygen species (ROS)-scavenging capability and high biocompatibility, also present a notable promoting effect in osteogenesis. BPNSs efficiently eliminate the intracellular ROS and, thus, protect the inherent homeostasis between cartilage matrix anabolism and catabolism. RNA sequencing results of BPNSs-treated OA chondrocytes further reveal the restoration of chondrocyte function, activation of antioxidant enzymes, and regulation of inflammation. Additional in vivo assessments solidly confirm that BPNSs inhibit cartilage degradation and prevent OA progression. Meanwhile, histological evaluation and microcomputed tomography (micro-CT) scanning analysis verify the satisfying disease-modifying effects of BPNSs on OA. Additionally, the excellent biocompatibility of BPNSs enables them as a competitive candidate for OA treatment. This distinct disease-modifying treatment of OA on the basis of BPNSs provides an insight and paradigm on the dual-functional treatment strategy focusing on both cartilage degradation and subchondral bone lesion in OA and explores a broader biomedical application of BPNS nanomedicine in orthopedics.

Stimulation of insulin secretion by glucose and other secretagogues from pancreatic islet beta-cells is mediated by multiple signaling pathways. Rac1 is a member of Rho family GTPases regulating cytoskeletal organization, and recent evidence also implicates Rac1 in exocytotic processes. Herein, we report that exposure of insulin-secreting (INS) cells to stimulatory glucose concentrations caused translocation of Rac1 from cytosol to the membrane fraction (including the plasmalemma), an indication of Rac1 activation. Furthermore, glucose stimulation increased Rac1 GTPase activity. Time course study indicates that such an effect is demonstrable only after 15 min stimulation with glucose. Expression of a dominant-negative Rac1 mutant (N17Rac1) abolished glucose-induced translocation of Rac1 and significantly inhibited insulin secretion stimulated by glucose and forskolin. This inhibitory effect on glucose-stimulated insulin secretion was more apparent in the late phase of secretion. However, N17Rac1 expression did not significantly affect insulin secretion induced by high K+. INS-1 cells expressing N17Rac1 also displayed significant morphological changes and disappearance of F-actin structures. Expression of wild-type Rac1 or a constitutively active Rac1 mutant (V12Rac1) did not significantly affect either the stimulated insulin secretion or basal release, suggesting that Rac1 activation is essential, but not sufficient, for evoking secretory process. These data suggest, for the first time, that Rac1 may be involved in glucose- and forskolin-stimulated insulin secretion, possibly at the level of recruitment of secretory granules through actin cytoskeletal network reorganization.