title: Collagen VI enhances cartilage tissue generation by stimulating chondrocyte proliferation.
abstract: Regeneration of human cartilage is inherently inefficient. Current cell-based approaches for cartilage repair, including autologous chondrocytes, are limited by the paucity of cells, associated donor site morbidity, and generation of functionally inferior fibrocartilage rather than articular cartilage. Upon investigating the role of collagen VI (Col VI), a major component of the chondrocyte pericellular matrix (PCM), we observe that soluble Col VI stimulates chondrocyte proliferation. Interestingly, both adult and osteoarthritis chondrocytes respond to soluble Col VI in a similar manner. The proliferative effect is, however, strictly due to the soluble Col VI as no proliferation is observed upon exposure of chondrocytes to immobilized Col VI. Upon short Col VI treatment in 2D monolayer culture, chondrocytes maintain high expression of characteristic chondrocyte markers like Col2a1, agc, and Sox9 whereas the expression of the fibrocartilage marker Collagen I (Col I) and of the hypertrophy marker Collagen X (Col X) is minimal. Additionally, Col VI-expanded chondrocytes show a similar potential to untreated chondrocytes in engineering cartilage in 3D biomimetic hydrogel constructs. Our study has, therefore, identified soluble Col VI as a biologic that can be useful for the expansion and utilization of scarce sources of chondrocytes, potentially for autologous chondrocyte implantation. Additionally, our results underscore the importance of further investigating the changes in chondrocyte PCM with age and disease and the subsequent effects on chondrocyte growth and function.
authors.affiliation: 1 Department of Orthopedic Surgery, Stanford University , Stanford, California.
authors.forename: Piera
authors.initials: P
authors.lastname: Smeriglio
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Dhulipala
authors.forename: Janice H
authors.initials: JH
authors.lastname: Lai
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Goodman
authors.forename: Jason L
authors.initials: JL
authors.lastname: Dragoo
authors.forename: Robert L
authors.initials: RL
authors.lastname: Smith
authors.forename: William J
authors.initials: WJ
authors.lastname: Maloney
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Nidhi
authors.initials: N
authors.lastname: Bhutani
mesh_terms: D000328:Adult; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D024142:Collagen Type VI / Q000494:pharmacology*; D006801:Humans; D008297:Male; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D024142:Collagen Type VI