Ciliary parathyroid hormone signaling activates transforming growth factor-β to maintain intervertebral disc homeostasis during aging

© 2018 The Author(s). Degenerative disc disease (DDD) is associated with intervertebral disc degeneration of spinal instability. Here, we report that the cilia of nucleus pulposus (NP) cells mediate mechanotransduction to maintain anabolic activity in the discs. We found that mechanical stress promotes transport of parathyroid hormone 1 receptor (PTH1R) to the cilia and enhances parathyroid hormone (PTH) signaling in NP cells. PTH induces transcription of integrin αvβ6 to activate the transforming growth factor (TGF)-β-connective tissue growth factor (CCN2)-matrix proteins signaling cascade. Intermittent injection of PTH (iPTH) effectively attenuates disc degeneration of aged mice by direct signaling through NP cells, specifically improving intervertebral disc height and volume by increasing levels of TGF-β activity, CCN2, and aggrecan. PTH1R is expressed in both mouse and human NP cells. Importantly, knockout PTH1R or cilia in the NP cells results in significant disc degeneration and blunts the effect of PTH on attenuation of aged discs. Thus, mechanical stress-induced transport of PTH1R to the cilia enhances PTH signaling, which helps maintain intervertebral disc homeostasis, particularly during aging, indicating therapeutic potential of iPTH for DDD

The timing of surgical staging has a significant impact on the complications and functional outcomes of adult spinal deformity surgery

To our knowledge, the effect of the staging regimen on the surgical outcome in patients undergoing combined anterior/posterior surgery for the treatment of spinal deformity has not been previously studied. To compare outcomes of anterior/posterior surgery for adult spinal deformity staged less than 21 days apart versus those 21 or more days apart. A retrospective comparison study. Patients aged 40 years or older who underwent combined anterior/posterior fusions for spinal deformities. Self-reported measures, physiological measures, and functional measures. We retrospectively reviewed prospectively collected data for 63 consecutive patients (50 females and 13 males) older than 40 years who underwent combined anterior/posterior fusions for spinal deformities and who had a minimum of 2-year follow-up. We divided them into those who had surgery staged less than 21 days apart (Group 1, N=29) and those who had surgery staged 21 or more days apart (Group 2, N=34). The groups were not statistically different in age; preoperative American Society of Anesthesiologists, Scoliosis Research Society-22 (SRS-22) patient questionnaire, and Oswestry Disability Index (ODI) scores; number of previous surgeries; number of levels fused; or total operative time. Hotelling t square test and the chi-squared test were used to compare clinical and radiographic parameters, complications, and functional outcomes between groups (significance, p<.05). Compared with Group 1 patients, Group 2 (staged) patients had a lower total estimated blood loss (average, 4.5 L [range, 1.90–8.75 L] vs. 4 L [range, 1.8–10.1 L], respectively), fewer combined hospital days (average, 14 days [range, 7–70 days] vs. 12 days [range, 6–44 days], respectively), and fewer major complications (total, 10 [35%] vs. 6 [18%], respectively). Preoperative SRS-22 and ODI scores were significantly better in Group 2 than in Group 1 at 6 weeks (p<.001) and at final follow-up (p<.001), respectively. For patients who require both anterior and posterior surgery for spinal deformity correction, staging the two procedures 21 or more days apart decreases total perioperative transfusion requirements although significantly improving functional outcomes