RRC ID 63207
Author Li X, Chen S, Hu Z, Chen D, Wang J, Li Z, Li Z, Cui H, Dai G, Liu L, Wang H, Zhang K, Zheng Z, Zhan Z, Liu H.
Title Aberrant upregulation of CaSR promotes pathological new bone formation in ankylosing spondylitis.
Journal EMBO Mol Med
Abstract Pathological new bone formation is a typical pathological feature in ankylosing spondylitis (AS), and the underlying molecular mechanism remains elusive. Previous studies have shown that the calcium-sensing receptor (CaSR) is critical for osteogenic differentiation while also being highly involved in many inflammatory diseases. However, whether it plays a role in pathological new bone formation of AS has not been reported. Here, we report the first piece of evidence that expression of CaSR is aberrantly upregulated in entheseal tissues collected from AS patients and animal models with different hypothetical types of pathogenesis. Systemic inhibition of CaSR reduced the incidence of pathological new bone formation and the severity of the ankylosing phenotype in animal models. Activation of PLCγ signalling by CaSR promoted bone formation both in vitro and in vivo. In addition, various inflammatory cytokines induced upregulation of CaSR through NF-κB/p65 and JAK/Stat3 pathways in osteoblasts. These novel findings suggest that inflammation-induced aberrant upregulation of CaSR and activation of CaSR-PLCγ signalling in osteoblasts act as mediators of inflammation, affecting pathological new bone formation in AS.
Volume 12(12)
Pages e12109
Published 2020-12-7
DOI 10.15252/emmm.202012109
PMID 33259138
PMC PMC7721361
MeSH Animals Bone Development* Bone and Bones / metabolism* Bone and Bones / pathology Female Humans Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Inbred DBA Osteoblasts / metabolism Osteoblasts / pathology Osteogenesis Receptors, Calcium-Sensing / genetics Receptors, Calcium-Sensing / metabolism* Spondylitis, Ankylosing / metabolism* Spondylitis, Ankylosing / pathology* Up-Regulation*
IF 8.821
Human and Animal Cells ATDC5(RCB0565)