Naproxen affects osteogenesis of human mesenchymal stem cells via regulation of Indian hedgehog signaling molecules

Introduction: We previously showed that type X collagen, a marker of late stage chondrocyte hypertrophy (associated with endochondral ossification), is constitutively expressed by mesenchymal stem cells (MSCs) from osteoarthritis patients and this may be related to Naproxen (Npx), a nonsteroidal anti-inflammatory drug used for therapy. Hedgehog (HH) signaling plays an important role during the development of bone. We tested the hypothesis that Npx affected osteogenic differentiation of human MSCs through the expression of Indian hedgehog (IHH), Patched-1 (PTC1) and GLI family members GLI1, GLI2, GLI3 in vitro. Methods: MSCs were cultured in osteogenic differentiation medium without (control) or with 0.5 mu M Npx. The expression of collagen type X, alpha 1 (COL10A1), alkaline phosphatase (ALP), osteopontin (OPN), osteocalcin (OC), collagen type I, alpha 1 (COL1A1) was analyzed with real-time reverse transcription (RT) PCR, and the ALP activity was measured. The osteogenesis of MSCs was monitored by mineral staining and quantification with alizarin red S. To examine whether Npx affects osteogenic differentiation through HH signaling, the effect of Npx on the expression of IHH, GLI1, GLI2, GLI3 and PTC1 was analyzed with real-time RT PCR. The effect of cyclopamine (Cpn), a HH signaling inhibitor, on the expression of COL10A1, ALP, OC and COL1A1 was also determined.Results: When MSCs were cultured in osteogenic differentiation medium, Npx supplementation led to a significant decrease in ALP gene expression as well as its activity, and had a tendency to decrease mineral deposition. It also decreased the expression of COL1A1 significantly. In contrast, the gene expression of COL10A1 and OPN were upregulated significantly by Npx. No significant effect was found on OC expression. The expression of IHH, PTC1, GLI1, and GLI2 was increased by Npx, while no significant difference was observed on GLI3 expression. Cpn reversed the effect of Npx on the expression of COL10A1, ALP, OPN and COL1A1. Conclusions: These results indicate that Npx can affect gene expression during osteogenic differentiation of MSCs, and downregulate mineral deposition in the extracellular matrix through IHH signaling. Therefore, Npx could affect MSC-mediated repair of subchondral bone in OA patients

Unilateral laminotomy with bilateral spinal canal decompression: systematic review of outcomes and complications

Abstract Background Unilateral laminotomy with bilateral spinal canal decompression has gained popularity recently. Aim To systematically review the literature of unilateral laminotomy with bilateral spinal canal decompression for lumbar spinal stenosis (LSS) aiming to assess outcomes and complications of the different techniques described in literature. Methods On August 7, 2022, Pubmed and EMBASE were searched by 2 reviewers independently, and all the relevant studies published up to date were considered based on predetermined inclusion and exclusion criteria. The subject headings “unilateral laminotomy”, “bilateral decompression” and their related key terms were used. The Preferred Reporting Item for Systematic Reviews and Meta-Analyses statement was used to screen the articles. Results A total of seven studies including 371 patients were included. The mean age of the patients was 69.0 years (range: 55–83 years). The follow up duration ranged from 1 to 3 years. Rate of postoperative pain and functional improvement was favorable based on VAS, JOA, JOABPEQ, RMDW, ODI and SF-36, for example improved from a range of 4.2–7.5 preoperatively on the VAS score to a range of 1.4–3.0 postoperatively at the final follow up. Insufficient decompression was noted in 3% of the reported cases. The overall complication rate was reported at 18–20%, with dural tear at 3.6–9% and hematoma at 0–4%. Conclusion Unilateral laminotomy with bilateral decompression has favorable short- and mid-term pain and functional outcomes with low recurrence and complication rates. This, however, needs to be further confirmed in larger, long-term follow-up, prospective, comparative studies between open, and minimally invasive techniques