Fibrous dysplasia (FD) is a skeletal stem cell disease caused by mutations in the guanine nucleotide-binding protein, alpha-stimulating activity polypeptide (GNAS) gene, which results in the abnormal accumulation of cyclic adenosine monophosphate (cAMP) and hyperactivation of downstream signaling pathways. Parathyroid hormone-related protein (PTHrP) is secreted by the osteoblast lineage and is involved in various physiological and pathological activities of bone. However, the association between the abnormal expression of PTHrP and FD, as well as its underlying mechanism, remains unclear. In this study, we discovered that FD patient-derived bone marrow stromal cells (FD BMSCs) expressed significantly higher levels of PTHrP during osteogenic differentiation and exhibited greater proliferation capacity but impaired osteogenic ability compared to normal control patient-derived BMSCs (NC BMSCs). Continuous exogenous PTHrP exposure on the NC BMSCs promoted the FD phenotype in both in vitro and in vivo experiments. Through the PTHrP/cAMP/PKA axis, PTHrP could partially influence the proliferation and osteogenesis capacity of FD BMSCs via the overactivation of the Wnt/β-Catenin signaling pathway. Furthermore, PTHrP not only directly modulated cAMP/PKA/CREB transduction but was also demonstrated as a transcriptional target of CREB. This study provides novel insight into the possible pathogenesis involved in the FD phenotype and enhances the understanding of its molecular signaling pathways, offering theoretical evidence for the feasibility of potential therapeutic targets for FD.

Under the background of high-quality development, the support of fiscal policy is important for enterprises to achieve high-quality development. As a major initiative to promote the supply-side reform in China, can tax cut policy promote the high-quality development of enterprises? In order to explore this question, based on the data of China’s listed companies from 2015-2019, this paper finds that: (i) Tax cut policy can improve the total factor productivity of enterprises and empower their high-quality development. (ii) The impact is different for companies in different regions and firms with different nature of property rights. Tax cut policy can better promote the high-quality development for companies in central regions and state-owned enterprises in China. (iii) The optimization of business environment effectively strengthens the positive effect of tax cut policy on the enterprise high-quality development. The effect of tax cut policy on total factor productivity is more obvious for companies in better business environment.