Calcified Tissue International

The original version of this article unfortunately contained a mistake in one of the co-author's name. The co-author Cyrus Cooper's degree “FMedSci” was incorrectly tagged as family name. This has been corrected with this erratum.

The role of epidermal growth factor receptors (EGF-R) in osteogenic cell differentiation was investigated using preosteoblastic MC3T3-E1 (MC3T3) cells and osteoblast-like ROS 17/2.8 (ROS) cells. When cultured in the presence of β-glycerophosphate (GP) and ascorbic acid (AA), MC3T3 cells underwent spontaneous differentiation into osteoblasts which was confirmed as they expressed osteoblast markers such as alkaline phosphatase (ALP), bone sialoprotein (BSP) and osteocalcin (OC). Interestingly, the number of EGF-binding sites decreased during their differentiation into osteoblasts, and the osteogenic protein-1 (OP-1) treatment, which accelerated their differentiation, lowered the number of EGF-binding sites even further. On the other hand, ROS cells with high expression levels of osteoblast markers and no EGF-R, after being transfected with human EGF-R cDNA (EROS cells), expressed numerous EGF-binding sites as well as EGF-R mRNA and protein; in the process, they ceased to express osteoblast markers, indicating their dedifferentiation into osteoprogenitor cells. Both MC3T3 and EROS cells showed increased cell growth in response to EGF, whereas ROS cells did not. These results imply that the EGF/EGF-R system in osteogenic cells has a crucial function in osteoblast phenotype suppression and osteogenic cell proliferation.

Using the transmission electron microscope, we sought to describe the morphology of thallium sulfate-induced chondrodystrophy in chick embryos. There was cell death and degeneration in all zones of growth cartilage, but the cells and matrix of the hypertrophic zone were the most severely affected. Ultrastructural changes of the hypertrophic chondrocytes consisted of alteration of the cytoplasmic contents and of the intercellular matrix; the cell membrane was smooth and without cytoplasmic extensions. The cytoplasm was filled with dilated rough endoplasmic reticulum, vacuoles of varying sizes and contents, and lipidlike bodies with electron-dense granules; mineral crystals, collagen, and degenerating mitochondria were present. The matrix showed only spotty calcification and a reduced number of dense bodies, vesicles, and granules. The cells appeared to have failed to exteriorize cell products across the plasmalemma. Failure to exteriorize cell products and to form cytoplasmic processes reduced the number of potential nucleation sites for calcification. The ultrastructure of osteocytes was much less affected.

The effects of the bone resorbing hormone, parathyroid hormone (PTH), on the growth of malignant osteoblastic cells have been examined. The malignant osteoblastic cells were a clonal line (UMR 106) derived from a transplantable rat osteogenic sarcoma. The predominant effect of PTH at doses above 10−10 M was an inhibition of replication and DNA synthesis. Replication was decreased by PTH in both the presence or absence of serum and at various cell seeding densities. Both bovine PTH (1-84) and the synthetic hormone, human PTH (1-34), inhibited replication, but with bovine hormone being an order of magnitude more potent. The effects could be observed in as short a time as 6 hours with DNA synthesis and 24 hours with replication.

For decades researchers reported that pre-menopausal women who engage in extensive endurance exercise and have menstrual dysfunction can develop low bone mineral density (BMD) or osteoporosis. More recently, low energy availability has been recognized as the initiating factor for low BMD in these women. Furthermore, the relationship between low energy availability and poor skeletal health is not exclusive to women engaging in endurance exercise. Rather, both males and females commonly experience endocrine dysfunction resulting from low energy availability and high exercise levels that degrades skeletal health. Consequences to skeletal health can range from short-term changes in bone metabolism and increased risk of bone stress injuries to long-term consequences of low BMD, such as osteoporosis and related fragility fractures. The degree to which low energy availability degrades skeletal health may be dependent on the length and extent of the energy deficit. However, the complex relationships between under-fueling, short- and long-term skeletal consequences and the factors that mediate these relationships are not well described. In this review, we discuss the consequences of low energy availability on sex hormones and skeletal health in two highly-active populations—athletes and military trainees—and provide a summary of existing knowledge gaps for future study.