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Endocrine Abstracts (2020) 70 AEP143 | DOI: 10.1530/endoabs.70.AEP143

ECE2020 Audio ePoster Presentations Bone and Calcium (121 abstracts)

Osteocalcin may participate to the bone-parathyroid crosstalk through activation of the calcium-sensing receptor in human parathyroid adenomas

Chiara Verdelli 1 , Giulia Stefania Tavanti 1 , Riccardo Maggiore 2 , Gilberto Mari 2 , Veronica Sansoni 3 , Silvia Perego 3 , Leonardo Vicentini 4 , Paolo Dalino Ciaramella 5 , Giovanni Lombardi 3,6 & Sabrina Corbetta 7,8


1IRCCS Istituto Ortopedico Galeazzi, Laboratory of Experimental Endocrinology, Milan, Italy; 2Endocrine Surgery, IRCCS Ospedale San Raffaele, Milan, Italy; 3Laboratory of Experimental Biochemistry & Molecular Biology, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy; 4Endocrine Surgery, IRCCS Istituto Auxologico Italiano, Milan, Italy; 5Endocrinology Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; 6Poznań University of Physical Education, Poznan, Poland; 7Endocrinology and Diabetology Service, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy; 8University of Milan, Department of Biomedical, Surgical and Dental Sciences, Milan, Italy


Parathyroid glands regulate bone metabolism through PTH, while bone modulates parathyroid function through calcium and FGF23. Bone releases the matrix protein osteocalcin (OC), whose hormone function is increasingly evident. We tested the hypothesis that OC may modulate parathyroid function. The 6 hours-stimulation of human parathyroid cells derived from adenomas (PAds) (n = 5) with γ-carboxylated OC (GlaOC; 40–60 ng/ml) increased the expression levels of the PTH, CASR and CCND1genes, as well as of WNT/β-catenin member AXIN2. In PAds-derived cells (n = 4), GlaOC (60–80 ng/ml) incubation for 10 min, inhibited the basal phosphorylated ERK/total ERK ratio (pERK/ERK) and increased the basal phosphorylated AKT/total AKT ratio (pAKT/AKT) and active β-catenin. PhosphoERK/ERK, pAKT/AKT and active β-catenin were similarly modulated by the incubation with 60–80 ng/ml undercarboxylated OC (GluOC). OC is known to exert its biologic effects through the activation of the putative membrane receptor GPRC6A. GPRC6A transcripts and proteins were variably detected in human PAds (n = 10). Immunohistochemistry showed specific GPRC6A cytoplasmic staining in some cells and membrane staining in other cells scattered throughout the parenchyma, both in normal and tumor parathyroids. Immunofluorescence detected colocalization of GPCR6A with PTH and GCM2. GPCR6A is a homolog of the calcium sensing receptor (CASR). CASR was variable expressed in the present series of PAds and it did not correlate with the GPRC6A expression. We investigated whether OC activates CASR, using HEK293 cells transiently transfected with GPRC6A (GPRC6A-HEK293) and with CASR (CASR-HEK293). Increasing GlaOC and GluOC (20–80 ng/ml) induced significant increases of pERK/ERK, decreases of pAKT/AKT, while active β-catenin was unaffected in GPRC6A-HEK293 cells. By contrast, GlaOC and GluOC inhibited the basal pERK/ERK levels and increased basal pAKT/AKT in CASR-HEK293 cells, resembling the effects detected in PAds-derived cells and suggesting that OC activates CASR in parathyroid cells. These patterns of response to OC were observed in presence of 1.5 mM extracellular calcium ([Ca2+]o). When CASR-HEk293 cells were cultured in presence of 5.0 mM [Ca2+]o, pERK/ERK levels were inhibited by GluOC, but not by GlaOC. By contrast, in [Ca2+]o-deprived medium, basal pERK/ERK levels were unaffected by both GlaOC and GluOC in both PAds-derived and CASR-HEK293 cells, while GlaOC and GluOC reverted their stimulatory effects on pERK/ERK, exerting inhibitory effects in GPRC6A-HEK293 cells, consistent with modulation of the biologic effects of OC by [Ca2+]o. These new data add OC to the bone-parathyroid cross-talk and suggest that CASR can be activated by OC with different intracellular signaling responses depending by [Ca2+]o.

Volume 70

22nd European Congress of Endocrinology

Online
05 Sep 2020 - 09 Sep 2020

European Society of Endocrinology 

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