SLPI is a critical mediator that controls PTH-induced bone formation

Osteoclastic bone resorption and osteoblastic bone formation/replenishment are closely coupled in bone metabolism. Anabolic parathyroid hormone (PTH), which is commonly used for treating osteoporosis, shifts the balance from osteoclastic to osteoblastic, although it is unclear how these cells are coordinately regulated by PTH. Here, we identify a serine protease inhibitor, secretory leukocyte protease inhibitor (SLPI), as a critical mediator that is involved in the PTH-mediated shift to the osteoblastic phase. Slpi is highly upregulated in osteoblasts by PTH, while genetic ablation of Slpi severely impairs PTH-induced bone formation. Slpi induction in osteoblasts enhances its differentiation, and increases osteoblast–osteoclast contact, thereby suppressing osteoclastic function. Intravital bone imaging reveals that the PTH-mediated association between osteoblasts and osteoclasts is disrupted in the absence of SLPI. Collectively, these results demonstrate that SLPI regulates the communication between osteoblasts and osteoclasts to promote PTH-induced bone anabolism.Morimoto A., Kikuta J., Nishikawa K., et al. SLPI is a critical mediator that controls PTH-induced bone formation. Nature Communications 12, 2136 (2021); https://doi.org/10.1038/s41467-021-22402-x

Severe panuveitis with relapsing polychondritis

Purpose: Relapsing polychondritis is a rare multiorgan disease characterized by repeated episodes of inflammation and deterioration of cartilages. We report a case of relapsing polychondritis that presented with severe panuveitis. Observations: A 53-year-old man visited our hospital because of ocular pain in both eyes of 2 weeks' duration. His best-corrected visual acuity was 20/20 in both eyes but he had severe hyperemia of the conjunctiva bilaterally. Inflammation in the anterior segment and vitreous opacity had been getting worse in his right eye. Systemic and topical treatments were not effective, and the visual acuity of the right eye was reduced to hand motion. Thus, pars plana vitrectomy with silicone oil tamponade was performed. After the operation, the vitreous opacities and white lesions in the retina were completely resolved. His visual acuity was improved to 20/20.Three years later, he developed dizziness and swelling of both auricles of his ears, and he was found to have sensorineural deafness. He was diagnosed with relapsing polychondritis after a laryngoscopic examination.Twelve months after the diagnosis, scleritis and panuveitis developed in his left eye, and his visual acuity fell to 20/2000. We performed pars plana vitrectomy with silicone oil tamponade on his left eye. After the vitrectomy, the inflammation of the left eye was resolved. Conclusion: and importance: Ophthalmologist should be aware that severe panuveitis with vitreous opacities may be the initial signs of relapsing polychondritis. In addition, vitrectomy was effective for the treatment of the ocular complications. Keywords: Relapsing polychondritis, Panuveitis, Type II collagen, Pars plana vitrectom