A pathological joint-liver axis mediated by matrikine-activated CD4^(+)T cells

The knee joint has long been considered a closed system.The pathological effects of joint diseases on distant organs have not been investigated.Herein,our clinical data showed that post-traumatic joint damage,combined with joint bleeding(hemarthrosis),exhibits a worse liver function compared with healthy control.With mouse model,hemarthrosis induces both cartilage degeneration and remote liver damage.Next,we found that hemarthrosis induces the upregulation in ratio and differentiation towards Th17 cells of CD4^(+)T cells in peripheral blood and spleen.Deletion of CD4^(+)T cells reverses hemarthrosis-induced liver damage.Degeneration of cartilage matrix induced by hemarthrosis upregulates serological type Ⅱ collagen(COL Ⅱ),which activates CD4^(+)T cells.Systemic application of a COL Ⅱ antibody blocks the activation.Furthermore,bulk RNAseq and single-cell qPCR analysis revealed that the cartilage Akt pathway is inhibited by blood treatment.Intra-articular application of Akt activator blocks the cartilage degeneration and thus protects against the liver impairment in mouse and pig models.Taken together,our study revealed a pathological joint-liver axis mediated by matrikine-activated CD4^(+)T cells,which refreshes the organ-crosstalk axis and provides a new treatment target for hemarthrosis-related disease.

Free or fixed state of nHAP differentially regulates hBMSC morphology and osteogenesis through the valve role of ITGA7

Nano-hydroxyapatite(nHAP)has been widely used in bone repair as an osteo-inductive and naturally-occurring material.However,the optimal applied form of nHAP and the underlying mechanisms involved remain unclear.Herein,to investigate into these,a range of corresponding models were designed,including three applied forms of nHAP(Free,Coating and 3D)that belong to two states(Free or fixed).The results indicate that when fixed nHAP was applied in the 3D form,optimal osteogenesis was induced in human bone marrow stem cells(hBMSCs)with increased bone volume via integrinα7(ITGA7)-mediated upregulation of the PI3K-AKT signaling pathway,while contrary results were observed with free nHAP.Ectopic osteogenesis experiments in mice subcutaneous transplantation model further confirmed the different tendencies of ITGA7 expression and osteogenesis of hBMSCs in free and fixed states of nHAP.Our results revealed that the two states of nHAP play a different regulatory role in cell morphology and osteogenesis through the valve role of ITGA7,providing cues for better application of nanoparticles and a potential new molecular target in bone tissue engineering.