Anti-MMP1 Catalytic Domain monoclonal antibody, clone MH25

Ultraviolet (UV) irradiation induces detrimental changes in human skin which result in photoaging. UV-induced intracellular changes cause degradation of extracellular matrix (ECM). UV-stimulated cleavage of collagen in ECM occurs via matrix metalloproteinases (MMPs). (+/-)-syringaresinol (SYR), a phytochemical which belongs to the lignan group of polyphenols, was investigated for its ability to reverse the UVA-induced changes in human HaCaT keratinocytes and dermal fibroblasts (HDFs) in vitro. Effect of SYR on UVA-induced changes was investigated by production and activation of MMPs and its transcriptional upstream effectors; mitogen-activated protein kinases (MAPKs) and pro-inflammatory mediators. Levels of expression were determined using ELISA, RT-PCR and immunoblotting. UVA irradiation stimulated the production of MMP-1 and inhibited collagen production. SYR treatment suppressed MMP-1 and enhanced collagen production in UVA-irradiated HaCaT keratinocytes and HDFs. SYR repressed the UV-induced phosphorylation of p38, ERK and JNK MAPKs in HaCaT keratinocytes while only suppressing JNK phosphorylation in HDFs. In addition, SYR was able to inhibit UVA-induced production of inflammatory cytokines; TNF-alpha, COX-2, IL-1 beta and IL-6. Moreover, SYR suppressed the activator protein-1 (AP-1), a heterodimer of phosphorylated transcription factors c-Jun and c-Fos. SYR-treatment decreased nuclear levels of activated c-Fos and c-Jun as a mechanism to inhibit UVA-induced transcriptional activities leading to MMP-1 production. In conclusion, current results demonstrated that SYR could inhibit UVA-induced upregulation of MMP-1 by suppressing MAPK/AP-1 signaling in HaCaT keratinocytes and HDFs. Therefore, SYR was suggested as a potential compound with antiphotoaging properties against UVA-induced skin aging.

Tendon tissues connect muscle to bone allowing the transmission of forces resulting in joint movement. Tendon injuries are prevalent in society and the impact on public health is of utmost concern. Thus, clinical options for tendon treatments are in demand, and tissue engineering aims to provide reliable and successful long-term regenerative solutions. Moreover, the possibility of regulating cell fate by triggering intracellular pathways is a current challenge in regenerative medicine. In the last decade, the use of magnetic nanoparticles as nano-instructive tools has led to great advances in diagnostics and therapeutics. Recent advances using magnetic nanomaterials for regenerative medicine applications include the incorporation of magnetic biomaterials within 3D scaffolds resulting in mechanoresponsive systems with unprecedented properties and the use of nanomagnetic actuators to control cell signaling. Mechano-responsive scaffolds and nanomagnetic systems can act as mechanostimulation platforms to apply forces directly to single cells and multicellular biological tissues. As transmitters of forces in a localized manner, the approaches enable the downstream activation of key tenogenic signaling pathways. In this minireview, we provide a brief outlook on the tenogenic signaling pathways which are most associated with the conversion of mechanical input into biochemical signals, the novel bio-magnetic approaches which can activate these pathways, and the efforts to translate magnetic biomaterials into regenerative platforms for tendon repair.