Hyaluronic Acid (HA), Platelet-Rich Plasm and Extracorporeal Shock Wave Therapy (ESWT) promote human chondrocyte regeneration in vitro and ESWT-mediated increase of CD44 expression enhances their susceptibility to HA treatment

Abstract

Novel strategies have been proposed for articular cartilage damage occurring during osteoarthritis (OA) and -among these- Extracorporeal Shock Wave Therapy (ESWT), intra-articular injections of Platelet-Rich Plasma (PRP) or Hyaluronic Acid (HA) revealed encouraging results. To investigate the possible mechanisms responsible for those clinical benefits, we established primary cultures of human chondrocytes derived from cartilage explants and measured the in vitro effects of ESW, PRP and HA therapies. After molecular/morphological cell characterization, we assessed those effects on the functional activities of the chondrocyte cell cultures, at the protein and molecular levels. ESWT significantly prevented the progressive dedifferentiation that spontaneously occurs during prolonged chondrocyte culture. We then attested the efficiency of all such treatments to stimulate the expression of markers of chondrogenic potential such as SOX9 and COL2A, to increase the Ki67 proliferation index as well as to antagonize the traditional marker of chondrosenescence p16INK4a (known as Cdkn2a). Furthermore, all our samples showed an ESW- and HA-mediated enhancement of migratory and anti-inflammatory activity onto the cytokine-rich environment characterizing OA. Taken together, those results suggest a regenerative effect of such therapies on primary human chondrocytes in vitro. Moreover, we also show for the first time that ESW treatment induces the surface expression of major hyaluronan cell receptor CD44 allowing the increase of COL2A/COL1A ratio upon HA administration. Therefore, this work suggests that ESW-induced CD44 overexpression enhances the in vitro cell susceptibility of human chondrocytes to HA, presumably favouring the repair of degenerated cartilage.

Extracorporeal shockwave treatment in knee osteoarthritis: therapeutic effects and possible mechanism

“…An in vitro study [53] explained that ESWT could increase the activity of chondrocytes through inducing the surface expression of major hyaluronan cell receptor CD44, which could allow the increase of Collagen type 2A/ Collagen type 1A (COL2A/COL1A) ratio when using HA, and this could enhance the cell susceptibility of chondrocytes to HA, favouring the repair of degenerated cartilage.…”

“…Liu et al [ 51 ] investigated the efficacy of ESWT combined with hyaluronic acid (HA) in patients with knee OA and used scoring scales, including a visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and knee injury and osteoarthritis outcome score (KOOS), to demonstrate the superiority of the combined approach relative to HA alone, since single HA treatment still has limited efficacy and accompanies a couple of adverse events [ 52 ]. An in vitro study [ 53 ] explained that ESWT could increase the activity of chondrocytes through inducing the surface expression of major hyaluronan cell receptor CD44, which could allow the increase of Collagen type 2A/ Collagen type 1A (COL2A/COL1A) ratio when using HA, and this could enhance the cell susceptibility of chondrocytes to HA, favoring the repair of degenerated cartilage. Another randomized controlled trial showed that ESWT can improve WOMAC and range of motion (ROM) better than kinesiotherapy (KIN) on knee OA [ 54 ].…”

Potential Implantable Nanofibrous Biomaterials Combined with Stem Cells for Subchondral Bone Regeneration

“…HAp increases the bioactivity of the scaffold by providing a source of calcium and phosphate ions that can be used by osteogenic cells to form bone [22]. Hyaluronic acid (HA) is an essential element of synovial fluid that preserves joint cartilage by lubricating and resisting shocks [23]; however, unfortunately, the intrinsically regenerative and damage-repair ability of human hyaline cartilage is restricted [24]. HA normally retains a constant concentration and adequate viscosity in articulations, but, when OA arises, the concentration of HA decreases, which exacerbates knee cartilage damage.…”

Association of Platelet-Rich Plasma and Auto-Crosslinked Hyaluronic Acid Microparticles: Approach for Orthopedic Application

“…Platelet-rich plasma (PRP) is a concentrate of platelets and other components of plasma, which has been widely used in regenerative medicine [1,2,3,4]. The regenerative potential of PRP is based on the release of growth factors that occurs with platelet degranulation.…”

“…More recently, PRP has been associated with high molecular weight hyaluronic acid (HA), mainly for orthopedic therapies [2,5]. HA is a glycosaminoglycan formed by a variable number of repeating units of D-glucuronic acid and N-acetylglucosamine.…”