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Clinical Reviews in Bone and Mineral Metabolism

, Volume 4, Issue 4, pp 233–257 | Cite as

Parathyroid hormone and bone cells

  • Richard Murrills
Article

Abstract

Parathyroid hormone has dual effects on bone cells, stimulating both bone resorption and bone formation. Almost all of the known effects of PTH on bone cells appear to be mediated through the PTH1 receptor (PTHR1). PTHR1 is found on several different cell types, including osteoblasts, osteoclasts, poorly-defined of receptor activator of osteoblastic NF-κB (RANKL) and osteoprotegerin (OPG) and induction of PGE, SDF-1 and perhaps IL-6 that acting with or through RANKL stimulate the differentiation and activity of osteoclasts. The bone formation effect results from PTH activating cells lining the bone surface to lay down new bone matrix increasing the proliferation of osteoblast precursors via release of growth factors FGF-2, TGF-β and IGF-1, increasing the differentiation of sub-populations of osteoblasts, and delaying the apoptosis of mature, matrix-secreting osteoblasts. Osteoclasts have also been implicated in mediating the bone-forming response to PTH through bone resorption-dependent and-independent mechanisms. Signaling of PTH in target cells is primarily through PTHR1 coupling to cAMP and Ca/PKC, but other pathways such as ERK/MAPK, Wnt and mechanical loading pathways may be activated or enhanced secondarily. Desensitization of PTHR1 has been proposed as an explanation for the time- and dose-dependence of PTHs catabolic and anabolic actions, a puzzle that has also been approached using RNA microarrays. PTH can have divergent effects on different bone envelopes i.e. trabecular, endosteal and periosteal, but these are incompletely explained by the current paradigms.

Key Words

Parathyroid hormone osteoblast osteoclast RANKL knockout mice bone formation bone resorption 

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Copyright information

© Humana Press Inc. 2006

Authors and Affiliations

  1. 1.Department of Osteoporosis, Women's Health and Musculoskeletal BiologyWyeth ResearchCollegeville

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