Decorin reduces hypertrophic scarring through inhibition of the TGF-β1/Smad signaling pathway in a rat osteomyelitis model

Abstract

Chronic osteomyelitis is a bone infection that results in hypertrophic scarring of the soft tissue surrounding the infected bone. This scarring can create functional problems and its treatment is challenging. The aim of the present study was to evaluate the efficacy of decorin in treating scar formation in osteomyelitis and the underlying mechanism of its action. A rat osteomyelitis model was used, and animals were divided into three groups, as follows: Group A (control), group B (osteomyelitis model) and group C (decorin-treated). X-ray scans, hematoxylin and eosin (H&E) staining and Masson's trichrome staining were performed to observe changes in femur and muscle tissue. In order to assess the role of the transforming growth factor β1 (TGF-β1)/Smad signaling pathway in scar formation in osteomyelitis, alterations in muscle tissue morphology and in the activation of key members of the TGF-β1/Smad signaling pathway were investigated in groups A and B. According to the results of H&E staining, evident fibrosis in muscle tissue were observed at days 14 and 28 in group B. Simultaneously, the expression levels of key members of the TGF-β1/Smad signaling pathway were increased. Subsequent to treatment with decorin in group C, scarring was reduced, and significant downregulation of collagen I, TGF-β1, phosphorylated (p)Smad2 and pSmad3 protein expression levels was observed at days 14 and 28 compared with the osteomyelitis group. In conclusion, these results suggest that activation of TGF-β1 may serve an important role in the formation of scars in osteomyelitis and that decorin can reduce scar formation in an osteomyelitis rat model through inhibition of the TGF-β1/Smad signaling pathway.

Serpine1 Knockdown Enhances MMP Activity after Flexor Tendon Injury in Mice: Implications for Adhesions Therapy

“…There are three approaches or classes of drugs to inhibit biological targets 39 . These include small molecular weight chemical compound (SMOL) inhibitors 20 , 45 , 46 , biologics (antibodies or other proteins that induce conformational changes to alter target function or favor the transition from active to latent forms) 3 , 5 , 47 – 50 and nucleic acids (acting through RNA interference mechanisms) 40 , 51 . Regardless of drug class, the route of administration is a critical factor in designing molecular therapeutics.…”

Proteoglycans in Biomedicine: Resurgence of an Underexploited Class of ECM Molecules

“…Adenovirus overexpression of IL-12 and decorin have demonstrated potent antitumor effects in a weakly immunogenic murine model of breast cancer (Oh et al, 2017a). Along similar lines, adenoviral overexpression of decorin and Granulocyte Macrophage Colony Stimulating Factor has shown anti-tumor potential in a model of murine colorectal cancer (Liu et al, 2017) (Wang et al, 2016). Shen and coworkers engineered a recombinant decorin fusion protein with an extended C-terminus comprised of a vascular homing peptide that recognizes inflamed blood vessels and penetrates deep into the vessel wall, known as CAR.…”

“…Ahmed et al (2014) showed that treatment of acute and chronic dorsal funicular spinal cord lesions (DFL) in adult rats with decorin resulted in a reduction in wound cavity area, suppression of inflammatory fibrosis, and dissolution of mature scars due to decorin's fibrolytic activity and neutralization of TGF-b1/2. In an independent study, decorin treatment reduced hypertrophic scarring through inhibition of the TGF-b1/Smad signaling pathway in a rat osteomyelitis model (Wang et al, 2016).…”

“…Dermatan sulfate Macular degeneration, diabetic retinopathy, diabetic macular edema (Devore et al, 2010) Corneal wound healing (Grisanti et al, 2005;Hill et al, 2018) Anti-scarring (Stuart et al, 2011;Ahmed et al, 2014;Wang et al, 2016) Oncosupression (Yang et al, 2015;Wang et al, 2016;Liu et al, 2017;Oh et al, 2017a) Abdominal aortic aneurysm (Shen et al, 2017) Vascular neointimal hyperplasia (Paderi et al, 2011;Scott and Panitch, 2014;Scott et al, 2017) Lumican Keratan sulfate Corneal wound healing (Chakravarti, 2002;Gesteira et al, 2017) Bacterial lung infections (Shao et al, 2012;Shao et al, 2013a) Scarring (Yeh et al, 2005;Liu et al, 2013;Yamanaka et al, 2013;Zhao et al, 2016) Melanoma (Zeltz et al, 2009;Pietraszek et al, 2013)…”

Insights into the key roles of epigenetics in matrix macromolecules-associated wound healing

“…The proteolytic modulation of collagen function is regulated my miRNAs miR-10a and miR-181c, which affect this process in hypertrophic scar fibroblasts by targeting PAI-1 and uPA and increasing MMP-1 levels [353]. Hypertrophic scars exhibit a lower expression of the PG decorin compared to healthy tissue [354] and it has been shown that decorin reduces hypertrophic scarring by modulating TGF-β functions [355,356]. Notably, miR-181b, a miRNA that is upregulated in hypertrophic scars, was shown to target decorin.…”