Generation of human nucleus pulposus cells from stem cells: First steps towards intervertebral disc regeneration.

Abstract

5% (95% CI 4%e6%) increased risk of back pain over the next 12 years, after adjusting for age, height, education status, physical activity and depression. Higher weight also predicted back pain risk over each 3 year survey interval (p<0.001). The effects of weight on back pain were most significant in those with body mass index 25 kg/m2 and were observed at all levels of physical activity. Inadequate physical activity and depression were independent predictors of back pain over the following 12 years (both p<0.001), after adjusting for above confounders. Conclusions: Back pain is common in community-based young adult women. Higher weight, inadequate levels of physical activity and depression were all independent predictors of back pain over the following decade. Furthermore, the adverse effects of weight on back pain were not mitigated by physical activity. Our findings highlight the role of both higher weight and physical inactivity in back pain among young adult women and suggest potential opportunities for future prevention.

Understanding embryonic development for cell‐based therapies of intervertebral disc degeneration: Toward an effort to treat disc degeneration subphenotypes

“…Therefore, NODAL shares type I and II receptors with Activin, also a member of the TGF‐β superfamily, and acts through a shared SMAD2/3 signaling pathway 44 . Accordingly, Activin is used to help differentiate pluripotent stem cells toward the notochord lineage 45‐48 . In addition, high levels of NODAL/SMAD2/3 signaling induce anterior fates, while lower levels of NODAL gradients drive mesoderm cell fate decisions in accordance with spatio‐temporal positioning 49 .…”

“…Thus, NODAL and WNT signaling pathways synergistically promote the formation of the primitive streak and drive cell lineage allocation within the mesoderm. Not surprisingly, activation of WNT signaling is also used to help differentiate pluripotent stem cells toward the notochord lineage 45‐48 …”

“…Correspondingly, ablation of the Noto ortholog ( flh ) in Zebrafish results in complete loss of the notochord 60 . Studies that aim to direct pluripotent stem cells into notochord‐like cells for tissue regeneration applications use FOXA2, T, and NOTO expression as markers to confirm that the cells are favoring a commitment toward the notochord lineage and not the paraxial and lateral plate mesoderm or endoderm lineages 45‐48 …”

“…44 Accordingly, Activin is used to help differentiate pluripotent stem cells toward the notochord lineage. [45][46][47][48] In addition, high levels of NODAL/SMAD2/3 signaling induce anterior fates, while lower levels of NODAL gradients drive mesoderm cell fate decisions in accordance with spatiotemporal positioning. 49 NODAL expression is maintained by WNT3 via direct regulation of the Nodal proximal epiblast enhancer, 43,49 and mice lacking WNT signaling fail to form the primitive streak and mesoderm.…”

“…Not surprisingly, activation of WNT signaling is also used to help differentiate pluripotent stem cells toward the notochord lineage. [45][46][47][48] The dorsal-ventral axis of the mesoderm is patterned to form the axial, paraxial, intermediate, and lateral plate mesoderm; indeed, the axial mesoderm gives rise to the notochord. Important determinants of the notochord identity include the forkhead box transcription factor FOXA2, also known as HNF-3β, the T-box transcription factor brachyury (T), and, acting downstream of FOXA2 and T, the homeobox transcription factor NOTO.…”