YTHDF2-regulated matrilin-3 mitigates post-reperfusion hemorrhagic transformation in ischemic stroke via the PI3K/AKT pathway.

Hemorrhagic transformation can complicate ischemic strokes after recanalization treatment within a time window that requires early intervention. To determine potential therapeutic effects of matrilin-3, rat cerebral ischemia-reperfusion was produced using transient middle cerebral artery occlusion (tMCAO); intracranial hemorrhage and infarct volumes were assayed through hemoglobin determination and 2,3,5-triphenyltetrazoliumchloride (TTC) staining, respectively. Oxygen-glucose deprivation (OGD) modeling of ischemia was performed on C8-D1A cells. Interactions between matrilin-3 and YTH N6-methyladenosine RNA binding protein F2 (YTHDF2) were determined using RNA immunoprecipitation assay and actinomycin D treatment. Reperfusion after tMCAO modeling increased hemorrhage, hemoglobin content, and infarct volumes; these were alleviated by matrilin treatment. Matrilin-3 was expressed at low levels and YTHDF2 was expressed at high levels in ischemic brains. In OGD-induced cells, matrilin-3 was negatively regulated by YTHDF2. Matrilin-3 overexpression downregulated p-PI3K/PI3K, p-AKT/AKT, ZO-1, VE-cadherin and occludin, and upregulated p-JNK/JNK in ischemic rat brains; these effects were reversed by LY294002 (a PI3K inhibitor). YTHDF2 knockdown inactivated the PI3K/AKT pathway, inhibited inflammation and decreased blood-brain barrier-related protein levels in cells; these effects were reversed by matrilin-3 deficiency. These results indicate that YTHDF2-regulated matrilin-3 protected ischemic rats against post-reperfusion hemorrhagic transformation via the PI3K/AKT pathway and that matrilin may have therapeutic potential in ischemic stroke.

Literature Analysis Regarding the Combination of Substances: Glucosamine + Chondroitin in the Treatment of Osteoarthritis.

An essential component of joint quality is cartilage. Therefore, the protection of this is a prerequisite for maintaining the condition of each joint. The assessment of the presence of articular cartilage is shown by X-ray of both joints in the standing position. Cartilage protection is possible for 1, 2 and 3 degree of cartilage damage according to the Kellgren and Lawrence scale.The challenge for the physician is to identify the cause of OA in accordance with the principles of Evidence Based Orthopedics/Traumatology, and not merely treat symptomatically, which is usually ineffective.In order to objectively present treatment methods, indications and the period of their implementation, it is biologically reasonable to refer to the needs of cartilage tissue resulting from the analysis of the causes of its damage and indications for justified methods of its protection.Biomechanical and biological elements are important in the process of implementing articular cartilage protection.The biomechanical elements are: limb axis disorders, differences in length, distortions at the level of the support quadrilateral, pelvic triangle and shoulder triangle, as well as balance disorders resulting from disturbances in the segmental proportion of the Fi number according to Leonardo da Vinci.There are many biological elements of the discussed disorder and they concern: the state of articular cartilage structure, matrix structure, matrix biophysical elements, molecular sponge mechanism, chondrocytes, cartilage nutrition and the severity of osteoarthritis (OA).The improvement of the conditions of the biological elements of damaged articular cartilage is considered fundamental and concerns the positive impact on numerous cartilage matrix proteins by chondroprotection. This element of treatment consists in the use of chondroitin sulphate and glucosamine as a drug, administered together in the appropriate dose and for a long time depending on the degree of degradation of the articular cartilage, usually from several to several months. The combination of chondroitin sulfate with glucosamine causes the activation of a much larger number of matrix proteins than each of the preparations separately.The pharmacokinetics of chondroitin sulfate and glucosamine are positive and favor their chondroprotective effect.The pharmacoproteomics of chondroitin sulfate and glucosamine administered together result from the activation of as many joint cartilage matrix proteins as possible. The development of proteomic techniques creates completely new therapeutic possibilities and is used to study the action of individual molecules.A clinically significant fact is that both chondroitin and glucosamine are natural, endogenous components of bone tissue and articular cartilage, so the use of both drugs is biologically compatible and results in numerous elements of cartilage protection.

Extraction and characterization of matrix protein from pacific oyster (Crassostrea gigs) shell and its anti-osteoporosis properties in vitro and in vivo.

Matrix protein is a kind of secretory protein that regulates the biomineralization of the bivalve shell. In this study, a water-soluble matrix protein (WSMP) from Pacific oysters (Crassostrea gigs) shell was isolated, and its structure was analyzed in detail, in addition to its anti-osteoporosis activity in vitro and in vivo. Results showed that WSMP was an acidic protein with an apparent molecular mass of 47 and 79 kDa and contained a glycoprotein structure. In vitro, the reduction of Tartrate-resistant acid phosphatase (TRAP) and deoxypyridinoline (DPD) indicated that osteoclast activity was inhibited compared with the model group. Moreover, the increased osteocalcin (OCN) and BMD levels suggested that the high osteoblast activity and bone mineralization was improved. SEM analysis of the femur showed that there were fewer bone pits in experimental groups, which was consistent with the above results. In vivo, WSMP promoted the expression of alkaline phosphatase (ALP) and osteogenic differentiation factor BMP-2 in osteoblasts. In addition, the activity of osteoclasts was inhibited by regulating the process of osteoclast differentiation induced by RANKL. Both in vitro and in vivo studies showed that WSMP could promote osteogenesis and inhibit osteoclast absorption, thus demonstrating their potential applications in osteoporosis.

[Biologic Reconstruction of Full Sized Cartilage Defects of the Hip: A Guideline from the DGOU Group "Clinical Tissue Regeneration" and the Hip Committee of the AGA]. / Biologische Rekonstruktion lokalisiert vollschichtiger Knorpelschäden des Hüftgelenks: Empfehlungen der Arbeitsgemeinschaft "Klinische Geweberegeneration" der DGOU und des Hüftkomitees der AGA.

Background Symptomatic pre-arthritic deformities such as femoroacetabular impingement (FAI) or hip dysplasia often lead to localised cartilage defects and subsequently to osteoarthritis. The present review of the working group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Trauma (DGOU) and the hip committee of the AGA (German speaking Society for Arthroscopy and Joint Surgery) provides an overview of current knowledge of the diagnosis and surgical treatment of cartilage defects, in order to infer appropriate therapy recommendations for the hip. Methods Review of FAI and resultant cartilage damage in the hip as reported in published study findings in the literature and discussion of the advantages and disadvantages of different surgical procedures to preserve the joint. Results Most published studies on the surgical treatment of cartilage damage in the hip report defects caused by cam-type FAI at the acetabulum. Development of these defects can be prevented by timely elimination of the relevant deformities. At present, current full-thickness cartilage defects are mostly treated with bone marrow-stimulating techniques such as microfracture (MFx), with or without a biomaterial, and matrix-assisted autologous chondrocyte transplantation (MACT). Osteochondral autologous transplantation (OAT) is not the treatment of choice for isolated full-thickness chondral defects at the hip, because of the unfavourable risk-benefit profile. Due to the relatively short history of cartilage repair surgery on the hip, the studies available on these procedures have low levels of evidence. However, it is already becoming obvious that the experience gained with the same procedures on the knee can be applied to the hip as well. For example, limited healing and regeneration of chondral defects after MFx can also be observed at the hip joint. Conclusions The cartilage surface of the acetabulum, where FAI-related chondral lesions appear, is considerably smaller than the weight-bearing cartilage surface of the knee joint. However, as in the knee joint, MACT is the therapy of choice for full-thickness cartilage defects of more than 1.5 - 2 cm2. Minimally invasive types of MACT (e.g. injectable chondrocyte implants) should be preferred in the hip joint. In cases where a single-stage procedure is indicated or there are other compelling reasons for not performing a MACT, a bone marrow-stimulating technique in combination with a biomaterial covering is preferable to standard MFx. For treatment of lesions smaller than 1.5 - 2 cm2 the indication for a single-stage procedure is wider. As with defects in the knee, it is not possible to determine a definite upper age limit for joint-preserving surgery or MACT in the hip, as the chronological age of patients does not necessarily correlate with their biological age or the condition of their joints. Advanced osteoarthritis of the hip is a contraindication for any kind of hip-preserving surgery. Long-term observations and prospective randomised studies like those carried out for other joints are necessary.

[Physical characterization of decellularized cartilage matrix for reconstructive rhinosurgery]. / Physikalische Charakterisierung dezellularisierter Knorpelmatrix zur Anwendung in der Rhinochirurgie.

BACKGROUND: The use of autologous auricular and rib cartilage for the reconstruction of nasal defects and deformities is associated with a number of disadvantages. The development of alternative materials is therefore the focus of intensive research. Recent studies demonstrated that decellularized cartilage is a promising material for cartilage tissue engineering. Hence, the aim of this study was to characterize the materials surface and cellular reactions to the decellularized cartilage matrix in long term-3D-culture. MATERIAL AND METHODS: Material geometry of decellularized cartilage was examined by microcomputed tomography as well as material characteristics by scanning and transmission electron microscopy. The expression of integrins on the surface of human chondrocytes was determined after seeding and migration into the scaffold. RESULTS: After decellularization an obvious enlargement of the matrix surface and an intensive interaction between the chondrocytes and the collagen matrix was observed. ITGA1 and ITGB1 were upregulated indicating chondrogenic differentiation. CONCLUSION: Therefore, decellularized porcine cartilage provides an optimal microstructure for human chondrocytes with respect to cell integration and matrix production. Thus, it offers promising characteristics for clinical application in reconstructive surgery.