Immunohistochemical analysis of transforming growth factor beta isoforms and their receptors in human cartilage from normal and osteoarthritic femoral heads.
ABSTRACT Osteoarthritis (OA) is characterized by erosion of cartilage and formation of osteophytes. Since transforming growth factor beta (TGF-beta) is known to be involved in chondrogenesis and osteogenesis, we studied by immunochemistry the expression of TGF-beta isoform types 1, 2, and 3 and their receptor types I and II in slightly and strongly altered areas of human OA cartilage and in osteophytes.
Specimens were collected from femoral heads at the time of hip arthroplasty, selecting osteophytic regions and areas of slight or severe degradation according to the Mankin score. Cryostat sections were prepared and submitted to immunohistochemistry using appropriate antibodies to TGF-beta(1-3) and TGF-beta receptors I and II.
TGF-beta1 expression was shown to be depressed in strongly degraded cartilage, compared to normal and slightly altered areas. TGF-beta2 was barely detectable in all samples studied. In osteophytes, a marked overexpression of TGF-beta1 and -beta3 was observed. An important decrease in TGF-beta receptor II was found in fibrillated cartilage areas.
The three major isoforms of TGF-beta are expressed in human OA cartilage, albeit the TGF-beta2 level is very low. Their expression patterns and the ratio of receptors I and II varies according to the degree of OA severity. The decrease in TGF-beta1 production and marked downregulation of receptor II in fibrillated cartilage may lead to reduced chondrocyte responsiveness to TGF-beta and contribute to the irreversibility of the disease. Overexpression of TGF-beta1 and -beta3 in osteophytes suggests that the two isoforms are involved in the formation of these structures.
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ABSTRACT: Transforming growth factor beta (TGFb) is a major signalling pathway in joints. This superfamilly is involved in numerous cellular processes in cartilage. Usually, they are considered to favor chondrocyte differentiation and cartilage repair. However, other studies show also deleterious effects of TGFb which may induce hypertrophy. This may be explained at least in part by alteration of TGFb signaling pathways in aging chondrocytes. This review focuses on the functions of TGFb in joints and the regulation of its signaling mediators (receptors, Smads) during aging and osteoarthritis.12/2014; 5(6):394-405. DOI:10.14336/AD.2014.0500394
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ABSTRACT: Interleukin-1β (IL-1β), a key-cytokine in osteoarthritis, impairs TGFβ signaling through TβRII down-regulation by increasing its degradation. Here, we investigated the molecular mechanism that controls TßRII fate in IL-1ß treated cells. Chondrocytes were treated with IL-1ß in the presence of different inhibitors. TßRII and Cav-1 expression were assayed by Western blot and RT-PCR. We showed that IL-1ß-induced degradation of TßRII is dependent on proteasome and on its internalization in caveolae. In addition, IL-1ß enhances Cav-1 expression, a major constituent of lipid raft. In conclusion, we enlighten a new mechanism by which IL-1ß antagonizes TGFß pathway and propose a model of TßRII turnover regulation upon IL-1ß treatment.Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 05/2012; 1823(5):983. DOI:10.1016/j.bbamcr.2012.02.017. · 5.30 Impact Factor
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ABSTRACT: Injection of platelet-rich plasma (PRP) is an evolving treatment option for various musculoskeletal injuries. There is basic scientific evidence that suggests that the various growth factors present in PRP can help to augment the body’s natural healing. There are also clinical studies suggesting efficacy for several conditions, particularly tendinopathy and osteoarthritis. This article reviews the definition and first uses of PRP, the basic scientific rationale for its use, and the basic science and evidence for its use in the treatment of tendon, joint, ligament, and muscle injuries. There are varying levels of evidence for and against the use of PRP for these types of injuries, and this article reviews studies that support as well as studies that refute the use of this new treatment. There are several studies that have assessed the basic science supportive of PRP treatments, as well as the clinical efficacy of this treatment in vivo. While the current evidence is mixed, several recent studies have demonstrated therapeutic benefit in the treatment of various tendinopathies and degenerative joint diseases of the knee. There are several factors that need to be addressed to elucidate whether PRP is truly effective. These include fully defining the PRP mixture (e.g. concentration, growth factor levels, presence of white cells and red cells, etc.), determining the optimal preparation and delivery of the PRP graft, calculating the appropriate number of injections for each specific pathologic process, and defining optimal post-procedure rehabilitation.03/2014; 2(1). DOI:10.1007/s40141-013-0039-5