Mitochondria transfer restores fibroblasts-like synoviocytes (FLS) plasticity in LPS-induced, in vitro synovitis model

BackgroundSynovitis (SI) is one of the most common and serious orthopedic diseases in horses of different age, breed and sex, which contributes to the development of osteoarthritis. The burden of SI includes economic loss and represents a real challenge for current veterinary health care. At the molecular level, fibroblasts-like synoviocytes (FLS) are recognized as major cell populations involved in SI pathogenesis. In the course of SI, FLSs are losing their protective and pro-regenerative cytological features, become highly proliferative and initiate various stress signaling pathways.MethodsFibroblast-like synoviocytes were treated with LPS in order to generate SI in vitro model. Mitochondria were isolated from peripheral blood derived mononuclear cells and co-cultured with FLS. After 24 h of culture, cells were subjected to RT-qPCR, western blot, cytometric and confocal microscopy analysis.ResultsMitochondrial transfer (MT) was observed in vitro studies using confocal microscopy. Further studies revealed, that MT to LPS-treated FLS reduced cell proliferation, modulated apoptosis and decreased inflammatory response. Overall, MT Resulted in the considerable recovery of recipient cells cytophysiological properties.ConclusionsPresented data provides evidence that mitochondria transfersignificantly modulate FLS proliferative and metabolic activity through improved mitochondrial biogenesis and dynamics in activated FLS. Obtained results for the first time demonstrate that horizontal MT might be considered as a therapeutic tool for synovitis treatment; however, further clinical studies are strongly required. Video abstract

Iron oxides nanoparticles (IOs) exposed to magnetic field promote expression of osteogenic markers in osteoblasts through integrin alpha-3 (INTa-3) activation, inhibits osteoclasts activity and exerts anti-inflammatory action

International audienceBackgroundPrevalence of osteoporosis is rapidly growing and so searching for novel therapeutics. Yet, there is no drug on the market available to modulate osteoclasts and osteoblasts activity simultaneously. Thus in presented research we decided to fabricate nanocomposite able to: (i) enhance osteogenic differentiation of osteoblast, (i) reduce osteoclasts activity and (iii) reduce pro-inflammatory microenvironment. As a consequence we expect that fabricated material will be able to inhibit bone loss during osteoporosis.ResultsThe α-Fe2O3/γ-Fe2O3 nanocomposite (IOs) was prepared using the modified sol–gel method. The structural properties, size, morphology and Zeta-potential of the particles were studied by means of XRPD (X-ray powder diffraction), SEM (Scanning Electron Microscopy), PALS and DLS techniques. The identification of both phases was checked by the use of Raman spectroscopy and Mössbauer measurement. Moreover, the magnetic properties of the obtained IOs nanoparticles were determined. Then biological properties of material were investigated with osteoblast (MC3T3), osteoclasts (4B12) and macrophages (RAW 264.7) in the presence or absence of magnetic field, using confocal microscope, RT-qPCR, western blot and cell analyser. Here we have found that fabricated IOs: (i) do not elicit immune response; (ii) reduce inflammation; (iii) enhance osteogenic differentiation of osteoblasts; (iv) modulates integrin expression and (v) triggers apoptosis of osteoclasts.ConclusionFabricated by our group α-Fe2O3/γ-Fe2O3 nanocomposite may become an justified and effective therapeutic intervention during osteoporosis treatment

Promotion through external magnetic field of osteogenic differentiation potential in adipose‐derived mesenchymal stem cells: Design of polyurethane/poly(lactic) acid sponges doped with iron oxide nanoparticles

International audienceRecently, iron oxide nanoparticles (IONPs) have gathered special attention in regenerative medicine. Owing to their magnetic and bioactive properties, IONPs are utilized in the fabrication of novel biomaterials. Yet, there was no report regarding thermoplastic polyurethane (TPU) and poly(lactic acid) (PLA) polymer doped with IONPs on osteogenic differentiation of mesenchymal stem cells. Thus the objectives of presented study was to: (a) fabricate magnetic TPU + PLA sponges doped with iron (III) oxide Fe2O3 nanoparticles; (b) investigate the effects of biomaterial and its exposition to static magnetic field (MF) on osteogenic differentiation, proliferation, and apoptosis in adipose‐derived mesenchymal stem cells (ASCs). TPU + PLA sponges were prepared using solvent casting technique while incorporation of the Fe2O3 nanoparticles was performed with solution cast method. RT‐PCR was applied to evaluate expression of osteogenic‐related genes and integrin's in cells cultured on fabricated materials with or without the stimulation of static MF. MF stimulation enhanced the expression of osteopontin and collagen type I while decreased expression of bone morphogenetic protein 2 in tested magnetic materials—TPU + PLA/1% Fe2O3 and TPU + PLA/5% Fe2O3. Therefore, TPU + PLA sponges doped with IONPs and exposure to MF resulted in improved osteogenic differentiation of ASC