Biomineralisation, the deposition of mineral onto a matrix, can be both a physiological and pathological process. Bone formation involves the secretion of an extracellular matrix (ECM) by osteoblasts and subsequent mineralisation of that matrix. It is regulated by a number of local and systemic factors and is necessary for maintenance of normal bone health. Conversely, mineralisation (or calcification) of soft tissues, including the vasculature, is detrimental to that tissue, leading to diseases such as arterial medial calcification (AMC). The mechanisms underlying AMC development are not fully defined, though it is thought that vascular smooth muscle cells (VSMCs) drive this complex, cell-mediated process. Similarly, AMC is regulated by a variety of enzymes and molecules, many of which have already been implicated in the regulation of bone mineralisation. This review will provide an overview of the similar, and sometimes opposing effects of these signalling molecules on the regulation of bone mineralisation and AMC.
Lucie E Bourne, Caroline P Wheeler-Jones, and Isabel R Orriss
Iain R Thompson, Annisa N Chand, Kim C Jonas, Jacky M Burrin, Mark E Steinhelper, Caroline P Wheeler-Jones, Craig A McArdle, and Robert C Fowkes
In the pituitary, C-type natriuretic peptide (CNP) has been implicated as a gonadotroph-specific factor, yet expression of the CNP gene (Nppc) and CNP activity in gonadotrophs is poorly defined. Here, we examine the molecular expression and putative function of a local gonadotroph natriuretic peptide system. Nppc, along with all three natriuretic peptide receptors (Npr1, Npr2 and Npr3), was expressed in both αT3-1 and LβT2 cells and primary mouse pituitary tissue, yet the genes for atrial-(ANP) and B-type natriuretic peptides (Nppa and Nppb) were much less abundant. Putative processing enzymes of CNP were also expressed in αT3-1 cells and primary mouse pituitaries. Transcriptional analyses revealed that the proximal 50 bp of the murine Nppc promoter were sufficient for GNRH responsiveness, in an apparent protein kinase C and calcium-dependent manner. Electrophoretic mobility shift assays showed Sp1/Sp3 proteins form major complexes within this region of the Nppc promoter. CNP protein was detectable in rat anterior pituitaries, and electron microscopy detected CNP immunoreactivity in secretory granules of gonadotroph cells. Pharmacological analyses of natriuretic peptide receptor activity clearly showed ANP and CNP are potent activators of cGMP production. However, functional studies failed to reveal a role for CNP in regulating cell proliferation or LH secretion. Surprisingly, CNP potently stimulated the human glycoprotein hormone α-subunit promoter in LβT2 cells but not in αT3-1 cells. Collectively, these findings support a role for CNP as the major natriuretic peptide of the anterior pituitary, and for gonadotroph cells as the major source of CNP expression and site of action.