PXL01 in sodium hyaluronate results in increased PRG4 expression: a potential mechanism for anti-adhesion

Abstract

PurposeTo investigate the anti-adhesive mechanisms of PXL01 in sodium hyaluronate (HA) by using the rabbit lactoferrin peptide, rabPXL01 in HA, in a rabbit model of healing tendons and tendon sheaths. The mechanism of action for PXL01 in HA is interesting since a recent clinical study of the human lactoferrin peptide PXL01 in HA administered around repaired tendons in the hand showed improved digit mobility.Materials and methodsOn days 1, 3, and 6 after tendon injury and surgical repair, reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) was used to assess mRNA expression levels for genes encoding the mucinous glycoprotein PRG4 (also called lubricin) and a subset of matrix proteins, cytokines, and growth factors involved in flexor tendon repair. RabPXL01 in HA was administered locally around the repaired tendons, and mRNA expression was compared with untreated repaired tendons and tendon sheaths.ResultsWe observed, at all time points, increased expression of PRG4 mRNA in tendons treated with rabPXL01 in HA, but not in tendon sheaths. In addition, treatment with rabPXL01 in HA led to repression of the mRNA levels for the pro-inflammatory mediators interleukin (IL)-1β, IL-6, and IL-8 in tendon sheaths.ConclusionsRabPXL01 in HA increased lubricin mRNA production while diminishing mRNA levels of inflammatory mediators, which in turn reduced the gliding resistance and inhibited the adhesion formation after flexor tendon repair.

Antimicrobial Peptides: An Emerging Category of Therapeutic Agents

“…PXL01 exhibits an inhibitory effect on the most important hallmarks of adhesion formation by repressing secretion of proinflammatory cytokines and promoting fibrinolysis (Nilsson et al, 2009). In addition, recent studies have shown that PXL01 regulates the production of the mucinous glycoprotein lubricin (Taguchi et al, 2009; Hayashi et al, 2013) in connection to surgery, which provides an additional mechanism to contribute to its adhesion-preventive properties (Edsfeldt et al, 2016). …”

Differentially Expressed Proteins in Intra Synovial Compared to Extra Synovial Flexor Tendon Grafts in a Rabbit Tendon Transplantation Model

“…Tenascin is found in abundance in tendons, both peri cellularly and around the collagen fiber bundles, and has been shown to be drastically upregulated upon injury. It has, furthermore, been postulated that the tenocytes respond to stress by producing Tenascin to increase the elasticity of the ECM surrounding them [ 32 ] and, through its effects, have anti-adhesive properties [ 33 , 34 ] at healing through blocking cell interactions with fibronectins and other matrix molecules [ 35 ]. The increased levels of Tenascin, and connected EGF-like and Fibronectin type-III domains in intra synovial tendon grafts compared to extra synovial grafts, may, therefore, play a role in anti-adhesive functions seen in intra synovial flexor tendon grafting.…”

TGF-β3 Regulates Adhesion Formation Through the JNK/c-Jun Pathway During Flexor Tendon Healing

“…Research on the mechanism of tendon injury showed that excessive load lead to the injury of tendon fibers, which would release a large number of inflammatory factors (35). With the continuous accumulation of inflammatory and collagen stimuli, the healing flexor tendon tissues secreted inflammatory cytokines such as IL-6, TNF-α, COX2, and IL-1β, and these cytokines promoted the accumulation of fibrin, and then lead to the formation of fiber adhesion (21,36). Inflammatory cytokines played a significant role in the process of tendon repair (36)(37)(38).…”