Osteoblastogenesis

An imbalance in the regulation of bone remodeling's two contrasting events, bone resorption and bone formation, results in many of the metabolic bone diseases, such as OSTEOPOROSIS.

Osteoporosis develops when the remodeling cycle, which is when the disruption of the bone resorption and bone formation occurs. The imbalance of the remodeling cycle causes osteoporosis. Hormones, cytokines, and paracrine stromal-cell interactions affect the osteoclast’s processes, which includes proliferation, maturation, fusion and activation. The osteoclasts are controlled by the interaction between several interleukins, tumor necrosis factor, transforming growth factor-beta, prostaglandin E2 and hormones. The glucocorticoid-induced osteoporosis is related to increased destruction of osteocytes. Glucocorticoid increase receptor activator of nuclear factor ligand (RANKL) effect and inhibit osteoprotegerin (OPG) production through

There are treatments that can help sustain quality of life for individuals with FOP. For example, steroids, such as glucocorticoids, can be used to help with relieving some mobility restrictions related to the overabundance of bone on muscles (10). More specifically, these help minimize the flare-up effects on heterotopic osteogenesis. Other possible treatments may involve the creation of inhibitors to block BMP pathway activity and signal transduction. Recently, Dorsomorphin, a signal transduction inhibitor, was found to disable type 1 receptors, and prevent phosphorylation of SMAD (10). However, it might be difficult to specifically target fibrodysplasia bone growth, without also altering normal bone growth and repair. The overlap in systems is a challenging obstacle to

This gene provides information for making a protein that regulates the transforming growth factor beta (TGF-β) signaling pathway. The TGF-β pathway regulates many processes, including cell growth and proliferation, the process by which cells mature to carry out special functions (differentiation), cell motility, and apoptosis. By attaching to certain proteins , the SKI protein blocks TGF-β signaling. The SKI protein is found in many cell types allover the body and appears to have a role in the development of many tissues, including the skull, other bones, skin, and brain.

Introduction: Osteoporosis is a disease that disproportionately affects postmenopausal women. It is an important disease for public health to address as it greatly contributes to frailty and risk of injury, largely due to fractures, and the associated burdens on the health care system. Literally translating to “porous bones”, osteoporosis occurs when bones lose their density, and the inner bone matrix becomes much more brittle (Figure 1).1,2 Health adult bones are in a constantly dynamic state, with living cells that multiply to grow and repair bones as we age. Bones structurally consist of a hard, calcified outer layer, and an inner matrix made of collagen and non-collagen proteins.3 Healthy bone mass, and the structure of this inner matrix, is maintained through processes called resorption and remodeling.1 Resorption occurs as some cells dissolve bone matrix for the body to reabsorb and reuse the minerals, and remodeling occurs simultaneously as other cells deposit new bone matrix proteins to replace the dissolved minerals. Each remodeling activity is associated with a slight net loss in bone mass, and as such, healthy adults achieve peak bone density in their early 20s, and bone density gradually declines thereafter.1,4

Garcia et al. (2013) carried out a study where a soluble form of human FGFR3 protein was employed to prevent FGF ligand from binding to the mutated FGFR3, and thus preventing the MAPK signaling pathway and STAT1 activation from being overactive. The soluble FGFR3 was injected into newborn mice twice a week for 3 weeks (Garcia et al. 2013). Restored growth plate bone chondrocytes maturation was seen and normal stature was conserved (Garcia et al. 2013). Curvature of the spine was also disappeared (Garcia et al.

Each year in the United States eight to forty children are born with malignant infantile osteopetrosis and one in every two hundred thousand people are affected by the adult form of osteopetrosis. Osteopetrosis is a rare genetic skeletal disorder in which there is an abnormal osteoclastic bone resorption resulting in patients who are more prone to fractures. This disorder “may be inherited as either a dominant or recessive trait and is marked by increased bone density, brittle bones, and, in some cases skeletal abnormalities” (NORD 2014). There are three major types of this condition. They are adult type autosomal dominant, malignant infantile type autosomal recessive, and the last is intermediate mild autosomal recessive.

     The first cases of osteogenesis imperfect date back to ancient times, with history of the condition becoming evident when an Egyptian infant mummified

While there has been some accord with respect to change of the proliferation capability of osteoblasts, some unfriendly impacts of FGF2 on the osteogenic separation and generalization have likewise been recognized.(Bosetti et al.) examined the striking of different FGFs (FGF2, FGF4, and FGF6) on the behavior of human-necessary osteoblasts. They examined that all FGFs activated in culture medium at 0.8 μM incited osteoblast enlargement yet stopped ALP motion and generalization. When it comes to Vitamin D, it was

In vitro: GW788388 inhibited both the TGF-β type I and type II receptor kinase activities, but not that of the related bone morphogenic protein type II receptor. In addition, GW788388 could blockTGF-β-induced Smad activation and target gene expression, while decrease epithelial–mesenchymal

Estrogen plays many functions in our body. One of its primary functions is associated with skeletal growth and bone homeostasis, including the inhibition of bone reabsorption. In women affected by estrogen deficiency, the decrease levels trigger an increased production of cell mediators such as cytokines (interleukin-1, interleukin-6, and TNF) leading to the stimulation and proliferation of osteoclast precursors. Decreased level of estrogen also contributes to osteoclast differentiation via RANK pathways. Therefore, even in the presence of osteoblastic activity as a compensatory mechanism, to produce new bone formation, this activity cannot keep up with the higher rate of bone loss, leading to early osteoporotic

Contradictory functions of osteopontin may be associated with Th1 and Th2 response and infiltration of inflammatory cells including different phenotypes of macrophages. In addition, since different forms of osteopontin in various tissues interact with distinct cell surface receptors and ECM proteins, osteopontin expressed by dissimilar cells or tissues may function differently. Therefore, identification of essential cellular sources of osteopontin in injured muscle and its’ influence on Th1 and Th2 responses is important.

Smads are structurally related intracellular signaling mediators, which are activated, among others, by serine/threonine kinase receptors to result in a phosphorylated Smad. The vertebrates found to possess altogether eight Smads (Smad1 to Smad8) with diverse roles in intracellular signaling and they depend for activation on extracellular ligands which bind to receptor extra-cellular domains (Derynck et al., 2003). The different Smads are specific for particular receptors. Smads-2 and -3 are activated through C-terminal phosphorylation by the TβRI and ActRIB, Smads1, -5 and -8 are activated by ALK-1, ALK2, ALK3 and ALK6 in response to BMPs of the TGF- β superfamily. Therefore it can be said that there are Smads that are more specific for TGF-β s and Smads that are BMP-specific. All in all, these five Smads have the common name R-Smads (receptor-Smads) and when activated they form a trimeric complex with a

The tight coupling of osteoclast and osteoblast activity continues bone remodeling or bone metabolism. Loss of this coupling might give rise to several skeletal pathologies characterized by increased or decreased osteoclast and osteoblast activities (21). Bone remodeling process is controlled by nervous regulation. Inputs from the central and peripheral nervous system feed into the already complex regulatory machinery controlling bone remodeling(22). Florent et al. has described the function of a number of “osteo-neuromediators” including norepinephrine and the beta 2-adrenergic receptor, Neuropeptide Y and the Y1 and Y2 receptors, endocannabinoids and the CB1 and CB2 receptors, as well as dopamine, serotonin and their receptors and transporters,

RANKL, its receptor RANK, and a decoy receptor, OPG, are three key molecules that regulate osteoclast recruitment and function. RANKL-binding to its receptor, RANK, expressed on osteoclast precursor cells elicits their differentiation and activation. On the other hand, OPG-binding to RANKL interrupts RANKL–RANK ligation; consequently, OPG inhibits the ability of RANKL to induce osteoclastogenesis. RANKL is not only been reported to be involved in physiological osteoclastogenesis, but also in pathological bone loss.(52,