Regenerative potential of mouse neonatal intervertebral disc depends on collagen crosslink density
Danielle N. D’Erminio,
Kaya A. Adelzadeh,
Ashley M. Rosenberg,
Robert J. Wiener,
Olivia M. Torre,
Emily D. Ferreri,
Philip Nasser,
Kevin D. Costa,
Woojin M. Han,
Alice H. Huang,
James C. Iatridis
Affiliations
Danielle N. D’Erminio
Department of Orthopedics, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Biomedical Engineering, The City College of New York at CUNY, New York, NY, USA
Kaya A. Adelzadeh
Department of Orthopedics, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Ashley M. Rosenberg
Department of Orthopedics, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Robert J. Wiener
Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Olivia M. Torre
Department of Orthopedics, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Emily D. Ferreri
Department of Orthopedics, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Philip Nasser
Department of Orthopedics, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Kevin D. Costa
Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Woojin M. Han
Department of Orthopedics, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Alice H. Huang
Department of Orthopedic Surgery, Columbia University, New York, NY, USA
James C. Iatridis
Department of Orthopedics, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Corresponding author
Summary: Intervertebral disc (IVD) defects heal poorly and can cause back pain and disability. We identified that IVD herniation injury heals regeneratively in neonatal mice until postnatal day 14 (p14) and shifts to fibrotic healing by p28. This age coincides with the shift in expansive IVD growth from cell proliferation to matrix elaboration, implicating collagen crosslinking. β-aminopropionitrile treatment reduced IVD crosslinking and caused fibrotic healing without affecting cell proliferation. Bulk sequencing on naive IVDs was depleted for matrix structural organization from p14 to p28 to validate the importance of crosslinking in regenerative healing. We conclude that matrix changes are key drivers in the shift to fibrotic healing, and a stably crosslinked matrix is needed for IVD regeneration.
