TY - JOUR
T1 - Molecular characterization of physis tissue by RNA sequencing
AU - Paradise, Christopher R.
AU - Galeano-Garces, Catalina
AU - Galeano-Garces, Daniela
AU - Dudakovic, Amel
AU - Milbrandt, Todd A.
AU - Saris, Daniel B.F.
AU - Krych, Aaron J.
AU - Karperien, Marcel
AU - Ferguson, Gabriel B.
AU - Evseenko, Denis
AU - Riester, Scott M.
AU - van Wijnen, Andre J.
AU - Noelle Larson, A.
PY - 2018/8/20
Y1 - 2018/8/20
N2 - The physis is a well-established and anatomically distinct cartilaginous structure that is crucial for normal long-bone development and growth. Abnormalities in physis function are linked to growth plate disorders and other pediatric musculoskeletal diseases. Understanding the molecular pathways operative in the physis may permit development of regenerative therapies to complement surgically-based procedures that are the current standard of care for growth plate disorders. Here, we performed next generation RNA sequencing on mRNA isolated from human physis and other skeletal tissues (e.g., articular cartilage and bone; n = 7 for each tissue). We observed statistically significant enrichment of gene sets in the physis when compared to the other musculoskeletal tissues. Further analysis of these upregulated genes identified physis-specific networks of extracellular matrix proteins including collagens (COL2A1, COL6A1, COL9A1, COL14A1, COL16A1) and matrilins (MATN1, MATN2, MATN3), and signaling proteins in the WNT pathway (WNT10B, FZD1, FZD10, DKK2) or the FGF pathway (FGF10, FGFR4). Our results provide further insight into the gene expression networks that contribute to the physis’ unique structural composition and regulatory signaling networks. Physis-specific expression profiles may guide ongoing initiatives in tissue engineering and cell-based therapies for treatment of growth plate disorders and growth modulation therapies. Furthermore, our findings provide new leads for therapeutic drug discovery that would permit future intervention through pharmacological rather than surgical strategies.
AB - The physis is a well-established and anatomically distinct cartilaginous structure that is crucial for normal long-bone development and growth. Abnormalities in physis function are linked to growth plate disorders and other pediatric musculoskeletal diseases. Understanding the molecular pathways operative in the physis may permit development of regenerative therapies to complement surgically-based procedures that are the current standard of care for growth plate disorders. Here, we performed next generation RNA sequencing on mRNA isolated from human physis and other skeletal tissues (e.g., articular cartilage and bone; n = 7 for each tissue). We observed statistically significant enrichment of gene sets in the physis when compared to the other musculoskeletal tissues. Further analysis of these upregulated genes identified physis-specific networks of extracellular matrix proteins including collagens (COL2A1, COL6A1, COL9A1, COL14A1, COL16A1) and matrilins (MATN1, MATN2, MATN3), and signaling proteins in the WNT pathway (WNT10B, FZD1, FZD10, DKK2) or the FGF pathway (FGF10, FGFR4). Our results provide further insight into the gene expression networks that contribute to the physis’ unique structural composition and regulatory signaling networks. Physis-specific expression profiles may guide ongoing initiatives in tissue engineering and cell-based therapies for treatment of growth plate disorders and growth modulation therapies. Furthermore, our findings provide new leads for therapeutic drug discovery that would permit future intervention through pharmacological rather than surgical strategies.
KW - Bone
KW - Cartilage
KW - Growth plate
KW - Physis
KW - RNA sequencing
KW - 22/4 OA procedure
UR - http://www.scopus.com/inward/record.url?scp=85047093347&partnerID=8YFLogxK
U2 - 10.1016/j.gene.2018.05.034
DO - 10.1016/j.gene.2018.05.034
M3 - Article
AN - SCOPUS:85047093347
SN - 0378-1119
VL - 668
SP - 87
EP - 96
JO - Gene
JF - Gene
ER -