Parathyroid Hormone Rapidly Stimulates Hyaluronan Synthesis by Periosteal Osteoblasts in the Tibial Diaphysis of the Growing Rat

Abstract

Short term treatment (3-24 h) with parathyroid hormone (PTH) stimulated the synthesis and accumulation of hyaluronan (HyA) in explant cultures of tibial diaphyses from young rats. PTH increased the overall HyA content of periosteum 5-fold, with the basal cambium layer exhibiting the greatest enhancement (ϳ8-fold). PTH increased the HyA content of cortical bone by 2-fold while not affecting the HyA content of bone marrow. PTH treatment greatly enhanced HyA staining throughout all layers of the periosteum, although its most dramatic effect occurred in the basal cambium layer. Here, unlike in the control tissue sections, nearly all cambium-lining osteoblasts stained intensely positive for HyA. PTH treatment enhanced the HyA staining of osteocytes in cortical bone tissue sections to the extent that the lacunocanalicular system became visualized. Three significant findings were revealed in this study. First, mature periosteal osteoblasts, under natural conditions, do not contain much HyA in their surrounding extracellular matrix but dramatically enhance their matrix HyA content when treated with PTH. Second, pre-osteocytes and osteocytes contain more HyA in their natural matrix than mature lining osteoblasts, and they appear to have functional PTH receptors because they responded to PTH treatment with an enhancement of HyA content. Finally, it was observed that the lining cells along the endosteal surface of the diaphysis did not stain strongly positive for HyA either naturally or when exposed to PTH treatment. This indicates that periosteal and endosteal osteoblastic cell populations exhibit metabolic differences in their extracellular matrix responses to PTH.

Parathyroid hormone (PTH) peptides through the regulation of hyaluronan metabolism affect osteosarcoma cell migration

“…Likewise, it has been reported that PTH (1-34) stimulates HA synthesis in calvarial explants, periosteal rat osteoblasts, and osteoblast-like rat cell lines (16,17) whereas, the effects of PTH (7-84) on osteoblastic cell HA metabolism have not been addressed so far. It is worthwhile to note that these previous reports had established a correlation between the effects of PTH (1-34) on osteoblastic lineage cell HA metabolism and differentiation status (16,17). In the present study, the effects of PTH (1-34) on HA metabolism were strongly dependent on the administration mode and the differentiation of the osteosarcoma cells, in accordance with previous findings (16,17).…”

“…It is worthwhile to note that these previous reports had established a correlation between the effects of PTH (1-34) on osteoblastic lineage cell HA metabolism and differentiation status (16,17). In the present study, the effects of PTH (1-34) on HA metabolism were strongly dependent on the administration mode and the differentiation of the osteosarcoma cells, in accordance with previous findings (16,17). Thus, intermittent treatment with PTH (1-34) increased the synthesis of HA and its' deposition in the pericellular matrix of MG-63 cells by stimulating their HAS2 expression.…”

“…Previously, PTH (1-84) has been reported to strongly stimulate HA production of both normal (15,16) and carcinogenic cells (17) of the osteoblastic lineage. Likewise, it has been reported that PTH (1-34) stimulates HA synthesis in calvarial explants, periosteal rat osteoblasts, and osteoblast-like rat cell lines (16,17) whereas, the effects of PTH (7-84) on osteoblastic cell HA metabolism have not been addressed so far.…”

“…Factors affecting HA metabolism, consequently, regulate the migration capacity of carcinoma cell lines (14). PTH has been reported to strongly stimulate the HA production of both normal (15,16) and carcinogenic cells of the osteoblastic lineage (17). It has been previously demonstrated that the antisense inhibition of HAS2, via reduction of HA accumulation and cell-associated matrix formation (18), inhibits MG-63 osteosarcoma cell proliferation, motility, and invasiveness.…”

RETRACTED: The periosteum

“…Because of ligament and tendon muscle attachments, and fibrocartilage, on some areas of the periosteal surface means that periosteal cells are exposed to the different physical environments in contrast to more frequently studied endosteal cells, which are bathed in hematopoietic marrow. Compared to endosteal osteoblasts, periosteal osteoblasts exhibit greater mechanosensitivity to strain, 61 a lower threshold of responsiveness to parathyroid hormone, 82 higher levels of expression of proteins such as periostin 55,90,123 and more estrogen α receptors. 21 These differences in threshold sensitivity to physical, hormonal, and mechanical stimuli may underlie the differences in periosteal and endosteal surface responses to therapy.…”