Wang Research

Yang Y, Lei H, Wang B. Effect of the PTHrP(1-34) analog abaloparatide on inducing chondrogenesis involves inhibition of intracellular reactive oxygen species production. Biochem Biophys Res Commun. 2019 Feb 19;509(4):960-965. https://pubmed.ncbi.nlm.nih.gov › 30654932

The synthetic PTHrP(1-34) analog abaloparatide (ABL) is a newly approved drug for osteoporosis therapy. Data from this paper show that the effect of ABL on stimulation of chondrogenesis is involved in its inhibition of intracellular reactive oxygen species generation. These novel findings support the use of ABL for the damaged cartilage regeneration.  

Pera T, Deshpande DA, Ippolito M, Wang B, Gavrila A, Michael JV, Nayak AP, Tompkins E, Farrell E, Kroeze WK, Roth BL, Panettieri RA Jr., Benovic JL, An SS, Dulin NO, Penn RB. Biased signaling of the proton-sensing receptor OGR1 by benzodiazepines. FASEB journal, 2018; 32(2):862-874. https://www.ncbi.nlm.nih.gov › articles › PMC5888400

Data from this paper show that lorazepam that acts as a Gq-biased allosteric modulator of OGR1, but not sulazepam that acts as a Gs-biased allosteric modulator of OGR1, promotes calcium mobilization. Alternatively, sulazepam significantly increases CRE-Luc activity (reflective of chronic cAMP/PKA signaling) in UMR cells, whereas lorazepam is without effect. These findings suggest sulazepam biases OGR1 signaling to “tune” PTH receptor signaling toward its therapeutic pathway.

Yang Y, Lei H, Qiang YW, Wang B. Ixazomib enhances parathyroid hormone (PTH)-induced beta-catenin/T-cell factor (TCF) signaling by dissociating beta-catenin from the PTH receptor. Mol Biol Cell, 2017, 28:1792-1803. https://www.ncbi.nlm.nih.gov › articles › PMC5491187

CRISPR/Cas9 genome-editing technology was used to knock out beta-catenin expression in osteoblast-like cell line. Data from this paper show that ixazomib enhances PTH stimulation of beta-catenin/TCF signaling via cAMP-dependent activation, and this effect is due to its separating beat-catenin from the PTH receptor. These findings provide evidence that ixazomib may be used to improve the therapeutic efficacy of PTH for the treatment of osteoporosis and other resorptive bone diseases.

Yang Y, Blair HC, Shapiro IM, Wang B. The proteasome inhibitor carfilzomib suppresses parathyroid hormone-induced osteoclastogenesis through a RANKL-mediated signaling pathway. The Journal of biological chemistry. 2015; 290(27):16918-28 https://www.ncbi.nlm.nih.gov › articles › PMC4505437

Date from this paper show that carfilzomib blocks PTH-induced osteoclast formation and bone resorption by its additional effect to inhibit RANKL-mediated I kappa B degradation and NF-kappa B activation in osteoclasts. This study showed for the first time that carfilzomib targets both osteoblasts and osteoclasts to suppress PTH-induced osteoclast differentiation and bone resorption.

Yang Y, Wang B. Disruption of β-catenin binding to parathyroid hormone (PTH) receptor inhibits PTH-stimulated ERK1/2 activation. Biochemical and biophysical research communications. 2015; 464(1):27-32. https://www.ncbi.nlm.nih.gov › articles › PMC4509838

Data from this paper show that PTH-stimulated ERK1/2 activation is mostly mediated through Gq/PLC signaling pathway. Transfection of mutant PTH receptor decreased PTH-induced ERK1/2 activation by inhibiting Gq-mediated signaling. This study shows for the first time that the interference of beta-catenin binding to PTH receptor inhibits PTH-stimulated ERK1/2 phosphorylation.