Parathyroid hormone: anabolic and catabolic actions on the skeleton

Abstract

Parathyroid hormone (PTH) is essential for the maintenance of calcium homeostasis through, in part, its actions to regulate bone remodeling. While PTH stimulates both bone formation and bone resorption, the duration and periodicity of exposure to PTH governs the net effect on bone mass, that is whether it is catabolic or anabolic. PTH receptor signaling in osteoblasts and osteocytes can increase the RANKL/OPG ratio, increasing both osteoclast recruitment and osteoclast activity, and thereby stimulating bone resorption. In contrast, PTH-induced bone formation is explained, at least in part, by its ability to downregulate SOST/sclerostin expression in osteocytes, permitting the anabolic Wnt signaling pathway to proceed. The two modes of administration of PTH, that is, continuous vs. intermittent, can regulate, in bone cells, different sets of genes; alternatively, the same sets of genes exposed to PTH in sustained vs. transient way, will favor bone resorption or bone formation, respectively. This article reviews the effects of PTH on bone cells that lead to these dual catabolic and anabolic actions on the skeleton.

Interleukin 27 (IL-27) Alleviates Bone Loss in Estrogen-deficient Conditions by Induction of Early Growth Response-2 Gene

“…It was observed that Ovx-induced micro-architectural deterioration was significantly prevented by IL-27 treatment in both femur and tibia bones. Effect of IL-27 on cortical parameters, like cortical thickness and bone area, was also determined because anabolic agents, like parathyroid hormone, lead to an increase in periosteal apposition (34). We observed increased cortical thickness and cortical bone area in Ovx mice treated with IL-27.…”

Prevention of breast cancer skeletal metastases with parathyroid hormone

“…At intermittent doses, PTH binds to the PTH1R and transiently regulates mRNAs encoding for transcription factors, cytokines, and growth factors via the cAMP/PKA signaling pathways, leading to an overall anabolic effect (49,51). In contrast, the OPG/RANKL/RANK pathway appears to be the prime mediator for the actions of continuous PTH (50,52). A DNA microarray study (53) of gene expression changes in rats treated with continuous or intermittent PTH for 7 days observed that both treatments resulted in gene expression patterns that matched the anticipated histomorphometric changes.…”

“…While continuous PTH exposure results in active bone resorption, intermittent PTH exposure favors bone formation (49,50). At intermittent doses, PTH binds to the PTH1R and transiently regulates mRNAs encoding for transcription factors, cytokines, and growth factors via the cAMP/PKA signaling pathways, leading to an overall anabolic effect (49,51).…”

Ariketa fisikoa hezur-dentsitate mineralaren suspertzaile

“…Osteozitoen eta osteoblastoen OPG-RANKL-RANK sistemaren modulatzaile gisa jokatzen du: alde batetik, RANKL errezeptorearen lotugaiaren bidez, osteoklastoen diferentziazioa sustatzen du, eta, bestetik, horien eragina erregulatzeko, RANKL eta bere hartzailearen (RANK) lotura apurtzen duen OPG-ren hartzailea sintetizatzen du. PTH hormonaren aktibazioa zelulaz kanpoko kaltzio-kontzentrazioaren araberakoa da [6]. Kontzentrazioa baxua denenean, PTH-ren sintesia aktibatu egiten da, eta, aldiz, kontzentrazioa altua denean, gelditu egiten da.…”