Nucleus pulposus phenotypic markers to determine stem cell differentiation: fact or fiction?
Progress in mesenchymal stem cell (MSC) based therapies for nucleus pulposus (NP) regeneration are hampered by a lack of understanding and consensus of the normal NP cell phenotype. Despite the recent consensus paper on NP markers, there is still a need to further validate proposed markers. This study aimed to determine whether an NP phenotypic profile could be identified within a large population of mature NP samples.qRT-PCR was conducted to assess mRNA expression of 13 genes within human non-degenerate articular chondrocytes (AC) (n=10) and NP cells extracted from patients across a spectrum of histological degeneration grades (n=71). qRT-PCR results were used to select NP marker candidates for protein expression analysis.Differential expression at mRNA between AC and non-degenerate NP cells was only observed for Paired Box Protein 1 (PAX1) and Forkhead box F1 (FOXF1). In contrast no other previously suggested markers displayed differential expression between non-degenerate NP and AC at mRNA level. PAX1 and FOXF1 protein expression was significantly higher in the NP compared to annulus fibrosus (AF), cartilaginous endplate (CEP) and AC. In contrast Laminin-5 (LAM-332), Keratin-19 (KRT-19) and Hypoxia Inducible Factor 1 alpha (HIF1α) showed no differential expression in NP cells compared with AC cells.A marker which exclusively differentiates NP cells from AF and AC cells remains to be identified, raising the question: is the NP a heterogeneous population of cells? Or does the natural biological variation during IVD development, degeneration state and even the life cycle of cells make finding one definitive marker impossible?
['Thorpe|Abbey A|AA|', 'Binch|Abbie L A|AL|', 'Creemers|Laura B|LB|', 'Sammon|Christopher|C|', 'Le Maitre|Christine L|CL|']
D002358:Cartilage, Articular D015815:Cell Adhesion Molecules D002454:Cell Differentiation D019902:Chondrocytes D051858:Forkhead Transcription Factors D005819:Genetic Markers D048091:Guided Tissue Regeneration D006801:Humans D051795:Hypoxia-Inducible Factor 1, alpha Subunit D007403:Intervertebral Disc D055959:Intervertebral Disc Degeneration D053539:Keratin-19 D045164:Mesenchymal Stem Cell Transplantation D059630:Mesenchymal Stem Cells D051761:Paired Box Transcription Factors D012333:RNA, Messenger
nucleus pulposus phenotypic markers regeneration FOXF1 Pathology Section stem cells PAX1