VPS35: Two Ways to Recycle the Parathyroid Hormone Receptor (PTH1R) in Osteoblasts
نویسنده
چکیده
The recombinant parathyroid hormone (PTH) Teriparatide is the only therapy for postmenopausal osteoporosis that increases bone mass (i.e., is anabolic). Its therapeutic action depends on a short “burst” of PTH in the circulation followed by a rapid return to normal levels; if PTH levels remain high, bone loss occurs (i.e., the effect is catabolic) (Frolik et al., 2003). This occurs because PTH not only stimulates the bone forming activity of osteoblasts, but also stimulates their ability to support osteoclast formation by producing RANKL. If PTH-induced RANKL production persists for longer than usual, anabolic intermittent PTH treatment can be switched to a catabolic effect (Walker et al., 2012). This may explain why PTH therapy is not effective in all patients, andwhy PTH anabolic effect is not sustainedwith long-term treatment. Identifying mechanisms that control how PTH signalling is terminated within the cell may provide new ways to design PTH-based therapies to overcome this problem. Three recent papers including work in EBiomedicine by Xiong et al. (Xiong et al., 2016; Chan et al., 2016; McGarvey et al., 2016) indicate that PTH receptor signalling duration is controlled by VPS35 and SNX27, two components of the retromer complex. PTH signals through PTH receptor (PTH1R). This G protein-coupled receptor is shared with PTHrP (PTH-related protein), a paracrine factor produced by osteoblasts essential for normal physiological bone
منابع مشابه
Osteoblastic expansion induced by parathyroid hormone receptor signaling in murine osteocytes is not sufficient to increase hematopoietic stem cells.
Microenvironmental expansion of hematopoietic stem cells (HSCs) is induced by treatment with parathyroid hormone (PTH) or activation of the PTH receptor (PTH1R) in osteoblastic cells; however, the osteoblastic subset mediating this action of PTH is unknown. Osteocytes are terminally differentiated osteoblasts embedded in mineralized bone matrix but are connected with the BM. Activation of PTH1R...
متن کاملMiR-125b inhibits stromal cell proliferation in giant cell tumor of bone by targeting parathyroid hormone 1 receptor
Objective(s):miR-125b has been identified as a tumor suppressor in many tumors, but its role in giant cell tumor (GCT) of bone remains poorly understood. The current study aimed to investigate the potential role and mechanism of miR-125b in GCT. Materials and Methods:Expression levels of miR-125b in GCT tissues were determined using RT-PCR. The cell proliferation was surveyed by direct cell coun...
متن کاملNHERF1 regulates parathyroid hormone receptor membrane retention without affecting recycling.
Na/H exchange regulatory factor-1 (NHERF1) is a PDZ protein that regulates trafficking of several G protein-coupled receptors. The phenotype of NHERF1-null mice suggests that the parathyroid hormone (PTH) receptor (PTH1R) is the principal GPCR interacting with NHERF1. The effect of NHERF1 on receptor recycling is unknown. Here, we characterized NHERF1 effects on PTH1R membrane tethering and rec...
متن کاملContinuous and intermittent exposure of neonatal rat calvarial cells to PTHrP (1-36) inhibits bone nodule mineralization in vitro by downregulating bone sialoprotein expression via the cAMP signaling pathway
The development and growth of the skeleton in the absence of parathyroid-hormone-related protein (PTHrP) is abnormal. The shortening of appendicular bones in PTHrP gene null mice is explained by an effect of PTHrP on endochondral bone growth. Whether or not PTHrP influences intramembranous ossification is less clear. The purpose of this study was to determine the effect of exogenous PTHrP on...
متن کاملContinuous and intermittent exposure of neonatal rat calvarial cells to PTHrP (1-36) inhibits bone nodule mineralization in vitro by downregulating bone sialoprotein expression via the cAMP
The development and growth of the skeleton in the absence of parathyroid-hormone-related protein (PTHrP) is abnormal. The shortening of appendicular bones in PTHrP gene null mice is explained by an effect of PTHrP on endochondral bone growth. Whether or not PTHrP influences intramembranous ossification is less clear. The purpose of this study was to determine the effect of exogenous PTHrP on in...
متن کامل