The Role Of Link Protein N-terminal Peptide In Chondroprogenitor Cell-Based Cartilage Repair And Regeneration

Objective:Articular cartilage defect and degeneration remain a challenge to orthopedic surgeons.Previous studies have shown that link-protein N-terminal peptide(LPP),which naturally exists in extracellular matrix of normal articular cartilage could induce the synthesis of proteoglycans and collagen type ? in cartilaginous cell types.Cartilage stem/progenitor cell(CSPC),an endogenous cell subpopulation which enjoys stem-cell like activities,plays a significant role in cartilage degeneration and the intrinsic regeneration,showing promising value in retaring the process of osteoarthritis.We hypothesized that LPP could be a stimulator for stem cell based-cartilage regeneration by affecting biological behaviors,including proliferation,migration,differentiation and cartilage repair abilily of CSPCMethods:Cartilage stem/progenitor cells were isolated from Sprague-Dawley rats knee cartilage through a fibronectin differential adhesion assay and then identified using multilineage differential potency analysis and surface markers detection.We evaluated the promoting effect of LPP on proliferation,migration and chondrogenic differentiation of CSPCs.The chondrogenic differentiation related genes and proteins that were altered by LPP were quantitated with q-PCR and Western Blot assays.Three-dimensional inductive culture of CSPC was conducted in the presence of TGF-?3 or LPP,and the pellets harvested were analyzed with safranine O staining,Toluidine Blue staining,and immunohistochemical assaysResults:LPP stimulated the proliferation of CSPC,accelerated the site-directional migration.Quantitative PCR and Western Blot demonstrated a higher expression of sox-9,collagen ? and aggrecan under the treatment of LPP.In the pellets formed by CSPC that were inducted to chondrogenesis,the synthesis of extracellular matrix,especially aggrecan was promoted and the pellets treated with 50ng/mL LPP showed more distinct chondroid differentiation characteristics than those with TGF-?3Conclusion:Link Protein N-terminal Peptide promotes the proliferation,migration and chondrogenic differentiation of cartilage stem/progenitor cells,which can effectively promote cartilage regeneration and endogenous repair.LPP demonstrates valuable application prospects in the chondroprogenitor cell-based articular cartilage repair and regeneration.