title: NELL-1 promotes cartilage regeneration in an in vivo rabbit model.
abstract: Repair of cartilage due to joint trauma remains challenging due to the poor healing capacity of cartilage and adverse effects related to current growth factor-based strategies. NELL-1 (Nel-like molecule-1; Nel [a protein strongly expressed in neural tissue encoding epidermal growth factor like domain]), a protein first characterized in the context of premature cranial suture fusion, is believed to accelerate differentiation along the osteochondral lineage. We previously demonstrated the ability of NELL-1 protein to maintain the cartilaginous phenotype of explanted rabbit chondrocytes in vitro. Our objective in the current study is to determine whether NELL-1 can affect endogenous chondrocytes in an in vivo cartilage defect model. To generate the implant, NELL-1 was incorporated into chitosan nanoparticles and embedded into alginate hydrogels. These implants were press fit into 3-mm circular osteochondral defects created in the femoral condylar cartilage of 3-month-old New Zealand White rabbits (n=10). Controls included unfilled defects (n=8) and defects filled with phosphate-buffered saline-loaded chitosan nanoparticles embedded in alginate hydrogels (n=8). Rabbits were sacrificed 3 months postimplantation for histological analysis. Defects filled with alginate containing NELL-1 demonstrated significantly improved cartilage regeneration. Remarkably, histology of NELL-1-treated defects closely resembled that of native cartilage, including stronger Alcian blue and Safranin-O staining and increased deposition of type II collagen and absence of the bone markers type I collagen and Runt-related transcription factor 2 (Runx2) as demonstrated by immunohistochemistry. Our results suggest that NELL-1 may produce functional cartilage with properties similar to native cartilage, and is an exciting candidate for tissue engineering-based approaches for treating diverse pathologies of cartilage defects and degeneration.
authors: Department of Bioengineering, University of California, Los Angeles, California 90095, USA.
authors: Ronald K
authors: RK
authors: Siu
authors: Janette N
authors: JN
authors: Zara
authors: Yaping
authors: Y
authors: Hou
authors: Aaron W
authors: AW
authors: James
authors: Jinny
authors: J
authors: Kwak
authors: Xinli
authors: X
authors: Zhang
authors: Kang
authors: K
authors: Ting
authors: Benjamin M
authors: BM
authors: Wu
authors: Chia
authors: C
authors: Soo
authors: Min
authors: M
authors: Lee
mesh_terms: D000464:Alginates / Q000737:chemistry; D000818:Animals; D016466:CHO Cells; D002135:Calcium-Binding Proteins; D002356:Cartilage / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D002417:Cattle; D006224:Cricetinae; D003412:Cricetulus; D004195:Disease Models, Animal; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D007150:Immunohistochemistry; D020007:Implants, Experimental; D007700:Kinetics; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D011817:Rabbits; D012038:Regeneration; D013194:Staining and Labeling
chemical_list: D000464:Alginates; D002135:Calcium-Binding Proteins; C104144:NELL1 protein, human; D009419:Nerve Tissue Proteins; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate