Osteoarthritis (OA) is a prevalent degenerative disease, which involves progressive and irreversible destruction of cartilage matrix. Despite efforts to reconstruct cartilage matrix in osteoarthritic ...joints, it has been a difficult task as adult cartilage exhibits marginal repair capacity. Here we report the identification of tankyrase as a regulator of the cartilage anabolism axis based on systems-level factor analysis of mouse reference populations. Tankyrase inhibition drives the expression of a cartilage-signature matrisome and elicits a transcriptomic pattern that is inversely correlated with OA progression. Furthermore, tankyrase inhibitors ameliorate surgically induced OA in mice, and stem cell transplantation coupled with tankyrase knockdown results in superior regeneration of cartilage lesions. Mechanistically, the pro-regenerative features of tankyrase inhibition are mainly triggered by uncoupling SOX9 from a poly(ADP-ribosyl)ation (PARylation)-dependent protein degradation pathway. Our findings provide insights into the development of future OA therapies aimed at reconstruction of articular cartilage.
Reduced amounts of collagen and fragmented collagen fibers are characteristics of aging skin. Recently, user-friendly, at-home personal aesthetic devices using light-emitting diode (LED) light have ...been used for cost-effective and safe skin improvement. However, to dramatically improve the skin via collagen repair, we need to develop an LED-responsive photosensitizer. Corneal collagen crosslinking uses ultraviolet light to activate riboflavin phosphate (RFP) and is used in ophthalmology. RFP is a biocompatible photosensitizer derived from vitamin B2. This study aimed to prove that RFP combined with blue light (BL) can increase collagen crosslinking density, improving its mechanical properties in skin tissue and enhancing skin elasticity. We confirmed the RFP-induced photo-crosslinking in pure collagen by studying changes in its dynamic modulus and matrix morphology using collagen hydrogels. We also measured the changes in the mechanical properties after applying photo-crosslinking on porcine skin. The Young’s modulus (1.07 ± 0.12 MPa) and tensile strength (11.04 ± 1.06 MPa) of the porcine skin after photo-crosslinking were 2.8 and 3.5 times better compared to those of normal porcine skin, respectively. Thus, photo-crosslinking through RFP and BL irradiation can be potentially used for skin improvement using aesthetic LED devices.
A clean and nontoxic one-step protein crosslinking reaction method induced by visible light was developed using eco-friendly chemicals, such as riboflavin phosphate (RFP), citric acid (CA), and ...polyols. In this study, oxygen radicals generated by blue light (BL)-irradiated RFP replace the conventional free thiol generatio step of the alkali condition. CA and polyol were used as crosslinkers and extenders, respectively, to enhance keratin crosslinking in hair. The new one-step crosslinking method was compared with the existing permanent hair waving treatment using thioglycolic acid (TGA). Compared to TGA treatment, the newly proposed crosslinking method induced minor damage to hair and keratin. In addition, the mechanical property changes were measured after crosslinking treatment on the hair. The tensile stress values and Young's moduli of the treated hair samples were approximately 1.3 and 2.2 times higher than untreated hair. The hair-setting effect was also confirmed by the changes in the radii of the hair fibers and the length of the hair tresses after crosslinking treatment. Therefore, we believe that the clean one-step crosslinking technology can be used to develop eco-friendly products for hair strengthening and setting.
•Clean one-step crosslinking of keratin is effective in strengthening and setting hair.•Keratin crosslinking is induced by exposure to blue light in the presence of RFP.•Citric acid and polyols form extender acts as a linker for keratin crosslinking.
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