In vitro regulation of proliferation and differentiation within a postnatal growth plate of the cranial base by parathyroid hormone‐related peptide (PTHrP)

Abstract

Parathyroid hormone-related peptide (PTHrP) is known to be an important regulator of chondrocyte differentiation in embryonic growth plates, but little is known of its role in postnatal growth plates. The present study explores the role of PTHrP in regulating postnatal chondrocyte differentiation using a novel in vitro organ culture model based on the ethmoidal growth plate of the cranial base taken from the postnatal day 10 mouse. In vitro the ethmoidal growth plate continued to mineralize and the chondrocytes progressed to hypertrophy, as observed in vivo, but the proliferative zone was not maintained. Treatment with PTHrP inhibited mineralization and reduced alkaline phosphatase (ALP) activity in the hypertrophic zone in the ethmoidal growth plates grown ex vivo, and also increased the proliferation of non-hypertrophic chondrocytes. In addition, exogenous PTHrP reduced the expression of genes associated with terminal differentiation: type X collagen, Runx2, and ALP, as well as the PTH/PTHrP receptor (PPR). Activation of the protein kinase A pathway using 8-Br-cAMP mimicked some of these pro-proliferative/anti-differentiative effects of PTHrP. PTHrP and PPR were found to be expressed within the ethmoidal growth plate using semi-quantitative PCR, and in other cranial growth plates such as the spheno-occipital and pre-sphenoidal synchondroses. These results provide the first functional evidence that PTHrP regulates proliferation and differentiation within the postnatal, cranial growth plate. J. Cell. Physiol. 219: 688-697, 2009. (c) 2009 Wiley-Liss, Inc.

The Paracrine Feedback Loop Between Vitamin D3 (1,25(OH)2D3) and PTHrP in Prehypertrophic Chondrocytes

“…Furthermore, the addition of PTHrP to ATDC5 cells in a prehypertrophic differentiation phase significantly downregulated the expression of the gene for the receptor of PTHrP, Pthr1 (Fig. 5A), which is also in line with previous reports (Weisser et al, 2002;Wealthall, 2009). This homologous downregulation of Pthr1 is possibly a measure to prevent overstimulation, but another explanation lies in the physiological role of PTHrP, namely, to prevent proliferative cells leaving the proliferating pool.…”

Recombinant Human Parathyroid Hormone Related Protein 1-34 and 1-84 and Their Roles in Osteoporosis Treatment

“…Osteoblasts are also target cells for locally produced PTHrP and circulating PTH, as these cells express PTHR1 [31]–[33]. Our previous results demonstrated that PTHrP stimulates osteogenic cell proliferation in rat marrow mesenchymal progenitor cells through protein kinase C-dependent activation of the Ras and MAPK signaling pathway [34].…”

Type II collagen peptide is able to accelerate embryonic chondrocyte differentiation: an association with articular cartilage matrix resorption in osteoarthrosis

“…Главной функцией суставного хряща является формирование поверхности, способной выдерживать большие нагрузки при малом трении для беспрепятственного движения сустава. Ранее мы предположили [16], что сохранение такой поверхности обеспечивается прекращением созревания сус-О Р И Г И Н А Л Ь Н Ы Е И С С Л Е Д О В А Н И Я НАУЧНО-ПРАКТИЧЕСКАЯ РЕВМАТОЛОГИЯ, 2010, № 6, 55-60 [4,[17][18][19][20][21][22][23]. Более того, разные части одной и той же молекулы могут оказывать двойное действие: например, аминотерминальные последовательности РТН подавляют экспрессию маркера гипертрофии -коллагена 10-го типа, тогда как срединный фрагмент РТН способен стимулировать его продукцию [6].…”