Obesity and the Regulation of Energy Balance

Endocrine Regulation of Energy Metabolism by the Skeleton

https://www.cell.com/cell/pdf/S0092-8674(00)81558-5.pdf

Leptin Inhibits Bone Formation through a Hypothalamic Relay: A Central Control of Bone Mass

The inorganic part of hard tissues (bones and teeth) of mammals consists of calcium phosphate, mainly of apatitic structure. Similarly, most undesired calcifications (i.e. those appearing as a result of various diseases) of mammals also contain calcium phosphate. For example, atherosclerosis results in blood-vessel blockage caused by a solid composite of cholesterol with calcium phosphate. Dental caries result in a replacement of less soluble and hard apatite by more soluble and softer calcium hydrogenphosphates. Osteoporosis is a demineralization of bone. Therefore, from a chemical point of view, processes of normal (bone and teeth formation and growth) and pathological (atherosclerosis and dental calculus) calcifications are just an in vivo crystallization of calcium phosphate. Similarly, dental caries and osteoporosis can be considered to be in vivo dissolution of calcium phosphates. On the other hand, because of the chemical similarity with biological calcified tissues, all calcium phosphates are remarkably biocompatible. This property is widely used in medicine for biomaterials that are either entirely made of or coated with calcium phosphate. For example, self-setting bone cements made of calcium phosphates are helpful in bone repair and titanium substitutes covered with a surface layer of calcium phosphates are used for hip-joint endoprostheses and tooth substitutes, to facilitate the growth of bone and thereby raise the mechanical stability. Calcium phosphates have a great biological and medical significance and in this review we give an overview of the current knowledge in this subject.

/pdf/biological-and-medical-significance-of-calcium-phosphates-4zx1s7sv8d.pdf

Biological and medical significance of calcium phosphates.

The strength and integrity of our bones depends on maintaining a delicate balance between bone resorption by osteoclasts and bone formation by osteoblasts. As we age or as a result of disease, this delicate balancing act becomes tipped in favor of osteoclasts so that bone resorption exceeds bone formation, rendering bones brittle and prone to fracture. A better understanding of the biology of osteoclasts and osteoblasts is providing opportunities for developing therapeutics to treat diseases of bone. Drugs that inhibit the formation or activity of osteoclasts are valuable for treating osteoporosis, Paget's disease, and inflammation of bone associated with rheumatoid arthritis or periodontal disease. Far less attention has been paid to promoting bone formation with, for example, growth factors or hormones, an approach that would be a valuable adjunct therapy for patients receiving inhibitors of bone resorption.

https://science.sciencemag.org/content/sci/289/5484/1508.full.pdf

Therapeutic approaches to bone diseases.

The molecular mechanisms controlling bone extracellular matrix (ECM) deposition by differentiated osteoblasts in postnatal life, called hereafter bone formation, are unknown. This contrasts with the growing knowledge about the genetic control of osteoblast differentiation during embryonic development. Cbfa1, a transcriptional activator of osteoblast differentiation during embryonic development, is also expressed in differentiated osteoblasts postnatally. The perinatal lethality occurring in Cbfa1-deficient mice has prevented so far the study of its function after birth. To determine if Cbfa1 plays a role during bone formation we generated transgenic mice overexpressing Cbfa1 DNA-binding domain (ΔCbfa1) in differentiated osteoblasts only postnatally. ΔCbfa1 has a higher affinity for DNA than Cbfa1 itself, has no transcriptional activity on its own, and can act in a dominant-negative manner in DNA cotransfection assays. ΔCbfa1-expressing mice have a normal skeleton at birth but develop an osteopenic phenotype thereafter. Dynamic histomorphometric studies show that this phenotype is caused by a major decrease in the bone formation rate in the face of a normal number of osteoblasts thus indicating that once osteoblasts are differentiated Cbfa1 regulates their function. Molecular analyses reveal that the expression of the genes expressed in osteoblasts and encoding bone ECM proteins is nearly abolished in transgenic mice, and ex vivo assays demonstrated that ΔCbfa1-expressing osteoblasts were less active than wild-type osteoblasts. We also show that Cbfa1 regulates positively the activity of its own promoter, which has the highest affinity Cbfa1-binding sites characterized. This study demonstrates that beyond its differentiation function Cbfa1 is the first transcriptional activator of bone formation identified to date and illustrates that developmentally important genes control physiological processes postnatally.

/pdf/a-cbfa1-dependent-genetic-pathway-controls-bone-formation-460bjxfums.pdf

A Cbfa1-dependent genetic pathway controls bone formation beyond embryonic development

Cbfa1 Contributes to the Osteoblast-specific Expression of type I collagen Genes

Cbfa1 as a regulator of osteoblast differentiation and function.

Functional Lecithin:Cholesterol Acyltransferase Deficiency and High Density Lipoprotein Deficiency in Transgenic Mice Overexpressing Human Apolipoprotein A-II

Jianhe Shen

Papers

Leptin Inhibits Bone Formation through a Hypothalamic Relay: A Central Control of Bone Mass

A Cbfa1-dependent genetic pathway controls bone formation beyond embryonic development

Cbfa1 Contributes to the Osteoblast-specific Expression of type I collagen Genes

Cbfa1 as a regulator of osteoblast differentiation and function.

Functional Lecithin:Cholesterol Acyltransferase Deficiency and High Density Lipoprotein Deficiency in Transgenic Mice Overexpressing Human Apolipoprotein A-II