Itt írjon a(z) BloodGlucoseBone-ról/ről
The effect of blood glucose on bone health
Glucose is the foundation of energy for most organisms on the planet. It makes sense that glucose will have an effect on normal bone development because it is the most essential energy biomolecule for organisms capable of respiration. As we know, bones have a powerful role in blood formation. Hence, bones will have a large capillary network for nutrients and products to leave/enter. Glucose’s main mode of transport is indeed the blood so the bones will have direct contact with fresh blood with glucose present. Our results concluded that diseases, such as diabetes mellitus, can cause fluctuation in blood glucose levels and hence bone health. Type 1 diabetes highlighted a result of lower bone mineral density (BMD) leading to a higher risk of osteoporosis. Whereas, type 2 diabetes causes increased BMD. However, the increased calcification is irregular and similarly to type 1, bone fractures were also a considerably high risk. This study revealed evidence to prove blood glucose has a role in bone metabolism.
Contents
1 - Introduction
The skeleton is often seen as an inert entity. However, old bone fragments are broken down and replaced with new skeleton tissue continuously. In fact, the skeleton replaces itself within ten years. New studies reveal a close connection between bone cells and blood glucose levels. This assignment aims to investigate bone health and how the effects of differing blood glucose levels can change the make-up of bones in the body.
2 - Normal Bone Development
During the early stages of embryonic development, the embryo’s skeleton consists of hyaline cartilage and a fibrous membrane. By the seventh week of embryonic life, the process of bone development, ossification (osteogenesis) starts. There are two different osteogenic pathways, intramembranous ossification and endochondral ossification. Bone is the same, regardless of what pathway produces it.
a.''Cartilage Templates''
Bone is a replaceable tissue, it uses a model tissue to lay down its mineral matrix. For skeletal development the most common template is cartilage. During foetal development a structure is laid down that determines where the bones will eventually form. This structure is a semi-solid matrix which is flexible and produced by chondroblasts, it contains water, collagen fibres, hyaluronic acid and chondroitin sulphate. Cartilage is avascular, therefore it does not have blood vessels that can supply nutrients and remove any waste product. These functions are carried out through diffusion through the matrix. This is why damaged cartilage does not repair itself as easily as other tissues. Through foetal and childhood growth and development, bone will form on this cartilaginous matrix. When the foetus is born the majority of the cartilage will be replaced with bone. The additional cartilage will be replaced with bone throughout childhood development and some remnants of cartilage will remain. The two stages of bone development through foetal development is Intramembranous ossification and Endochondral ossification. The four general categories of bones are long bones, short bones, flat bones, and irregular bones. Long bones include the clavicles, humeri, radii, ulnae, metacarpals, femurs, tibiae, fibulae, metatarsals, and phalanges. Short bones include the carpal and tarsal bones, patellae, and sesamoid bones. Flat bones include the skull, mandible, scapulae, sternum, and ribs. Irregular bones include the vertebrae, sacrum, coccyx, and hyoid bone. Flat bones form by membranous bone formation, whereas long bones are formed by a combination of endochondral and membranous bone formation. (Clarke, B., 2008.) Bone undergoes longitudinal and radial growth, modelling, and remodelling during life. Longitudinal and radial growth during growth and development occurs during childhood and adolescence. Longitudinal growth occurs at the growth plates, where cartilage proliferates in the epiphyseal and metaphyseal areas of long bones, before subsequently undergoing mineralization to form primary new bone. (Clarke, B., 2008.)
b.''Endochondral ossification''
Endochondral ossification is the type of bone ossification where bone tissue is created directly over the cartilage.
Bone develops by replacing hyaline cartilage. This does not become bone. Instead, the cartilage serves as a template to be entirely replaced by new bone. Endochondral ossification takes a much longer time than intramembranous ossification. Long bones and bones at the base of the skull form throughout this endochondral ossification. Development of endochondral bones initiates shortly after the formation of the limb bud with the condensation of loose mesenchyme, marked by expression of type II collagen. Condensing mesenchyme forms an anlage for the endochondral skeleton and can either branch or segment to form individual skeletal elements. Differentiation of condensing mesenchyme gives rise to a proliferating population of centrally localized type II collagen-expressing chondrocytes and more peripherally localized type I collagen-expressing perichondrial cells. At this stage, chondrocytes begin to elaborate a specialized extracellular matrix containing type II collagen. Midway between the ends of this elongated cartilaginous template, chondrocytes exit the cell cycle, hypertrophy, and begin to synthesize type X collagen in place of type II collagen. (Ornitz, D.M. and Marie, P.J., 2002) To synthesize bone, a centre of ossification forms in the mid-hypertrophic zone by neovascularization of the initially avascular cartilaginous template. The secretion and mineralization of a type I collagen-containing extracellular matrix is mediated by osteoblasts that are associated with the newly developed vasculature. As bones grow, this centre of ossification propagates toward the two epiphyseal plates. (Ornitz, D.M. and Marie, P.J., 2002)
3. - Effects of glucose and normal bone formation
Glucose has a huge effect on normal bone development, whether it be high or low level of glucose each have different negative effects on bone health. You can’t mention both high and low levels of glucose without mentioning the most important glucose related disease diabetes mellitus, but that will be spoken about later on. Glucose can directly affect bone mineral density (BMD) and calcification of bones. In a study bone calcification was investigated whether glucose affects osteoblastic calcium deposition. MC3T3-E1 ( osteoblast precursor cells obtained from the calvaria of mice) cells were incubated in media containing either a normal (5.5 mmol/L)[control] or a high glucose concentration (15 mmol/L) or mannitol (15 mmol/L). Osteoblast activity was measured by alkaline phosphatase (Bone specific alkaline phosphatase isoenzyme is elevated as a result of increased osteoblastic activity). The bone nodules were examined daily. During matrix maturation and formation cultures undergo a phase of increased calcium deposition. Results show that the size of the nodules was larger by up to four times in the high concentration of glucose but the shape was very irregular and distorted. Despite being much larger, the size of the calcified area relative to the size of the nodule was the same across the samples by percentage of mass that was calcified. However in the presence of glucose, the daily calcium uptake was sizably inhibited compared to the control and mannitol, see Graph 1. Therefore larger nodules were created but with less calcification. (E. Balint et al. 2001)Screen Shot 2018-04-24 at 11.00.52.png
