Working model of regulation of HSCs by the BM niche in β-thalassemia and rescue by PTH administration. In β-thalassemia, the lower levels of PTH negatively act via PTH receptors on osteolineage cells and MSCs, resulting in reduced trabecular bone and fewer MSCs. Thalassemic BM stromal cells show lower expression of the Notch-ligand JAG1, which is consistent with the reduced activation of the Notch pathway (activated NICD) in HSCs. Moreover, decreased OPN levels correlate with the increased cycling activity of HSCs, thus affecting their self-renewal capacity and causing the progressive exhaustion of the quiescent HSC pool. In vivo administration of PTH restores thalassemic trabecular bone and MSC frequency, enhancing JAG1 and OPN expression by the BM niche and thus rescuing HSC function.