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Statins are a class of drugs widely used in the treatment of cardiovascular diseases to reduce hypercholesterolemia, and involve an increased prevalence of osteoporosis. Several studies suggested that statin mediates stimulation of bone remodeling. One of the statin family members was first isolated from Penicillin citrium (mevastatin), and another later from Aspergillus terreus (lovastatin). Roles of statins are mediated by competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, such as inhibition of the mevalonate pathway. Statins have a potential antiinflammatory effect (IL-6), which may be related to promotion of bone growth and maintaining bone health. Statins in local use and general administration enhance osteoblastic differentiation and production of bone matrix proteins via bone morphogenetic protein 2 (BMP-2) signaling pathways. Clinical applications of statins have increasingly been reported for bone fractures and implant dentistry. The present review introduces biophysiological functions of the statin family in normal remodeling of bone tissues demonstrated by both in vivo and in vitro studies, and in promoting bone growth caused by osteoprotegerin production by statins with BMP-2.

Natriuretic peptides (NPs), guanylin, uroguanylin, heat-stable enterotoxin type a (STa), and the cystic fibrosis transmembrane conductance regulator (CFTR) are important regulators involving water and ionic balance in vertebrates. The present report points out the evolution of osmoregulatory systems and their effector organs, including the rectal glands of eels, frogs, and sharks; the salt glands of birds; and the salivary glands of mammals, including those of humans. Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), and the activity of their respective receptors in the organs of vertebrates were reported as biological characteristics of heart hormone. This review focuses on Cl-/HCO3- exchange activity in the salivary gland ducts and ductal basal cells that express NPs and related regulators. This report describes published histochemical findings on protein and mRNA expression in ductal basal cells and the biological significances of those findings with regard to the mammalian salivary gland duct system and a number of growth factors synthesized in the granular convoluted tubules (GCT).

The present paper provides a general review of the biophysiology of natriuretic peptides (NPs) in mammals. NPs, classified as hypotensive hormones, include atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP), as well as their receptors, which involve natriuretic and diuretic activity and also blood circulation and volume homeostasis. This review also summarizes the historical background of NP families and cyclic guanosine monophosphate (cGMP)-dependent protein kinase (cGK1) and their biological properties in cardiovascular tissues, heart diseases, renal functions and disease, respiratory and lung failure, gastrointestinal tissue, urogenital and reproductive organs, endocrine activities, the central nerve system, and bone tissue. ANP triggers natriuretic and diuretic activities in the kidney and alters the electrolyte balance via intestinal absorption of water and sodium ions. CNP is involved in promoting wound healing in arterial endothelial cells. The CNPR-related bone pathway plays a causal active role in bone anomalies, and is a regulator of longitudinal skeletal growth diseases such as achondroplasia. CNP-natriuretic receptor B (CNP/NPR-B) system has signifi cant role in the processes of enchondral ossification. Recently, osteocrin/musclin was discovered as belonging to the NP family; it binds with high affinity to NPR-C and plays a role in bone growth.

Salivary glands secrete saliva which contains mucins, antimicrobial substances and growth factors. Since epidermal growth factor (EGF) and nerve growth factor (NGF) were demonstrated in murine submandibular glands (SMGs), several growth factors and biologically-active peptides have been studied in the human or other mammalian salivary glands and saliva. These growth factors may have a functional role in cell migration, proliferation and maturation within not only salivary glands but also other organs. In the SMGs of mice and rats, EGF, NGF and other known growth factors are usually synthesized in granular convoluted tubule cells (GCT). However, human SMGs are devoid of GCT cells, and growth factors in human salivary glands are usually produced in striated ducts. These findings suggest an evolutionary trace of ductal cells in mammals. The present review describes expression patterns of the following salivary gland growth factors: nerve growth factor (NGF); transforming growth factor α and β (TGF-α/β) bone morphogenetic protein (BMP); insulin-like growth factor (IGF); fibroblastic growth factor (FGF); and somatostatin, as well as their receptors. This review also discusses their cell biological roles in pathophysiological conditions.