Molecular Mechanisms Involved in Hypoxia-Induced Alterations in Bone Remodeling

Abstract

Bone is crucial for the support of muscles and the protection of vital organs, and as a reservoir of calcium and phosphorus. Bone is one of the most metabolically active tissues and is continuously renewed to adapt to the changes required for healthy functioning. To maintain normal cellular and physiological bone functions sufficient oxygen is required, as evidence has shown that hypoxia may influence bone health. In this scenario, this review aimed to analyze the molecular mechanisms involved in hypoxia-induced bone remodeling alterations and their possible clinical consequences. Hypoxia has been associated with reduced bone formation and reduced osteoblast matrix mineralization due to the hypoxia environment inhibiting osteoblast differentiation. A hypoxic environment is involved with increased osteoclastogenesis and increased bone resorptive capacity of the osteoclasts. Clinical studies, although with contradictory results, have shown that hypoxia can modify bone remodeling.

Low bone mineral density and its related factors in adults with congenital heart disease in Vietnam: A cross‐sectional study

“…Polycythemia in adults with CHD is the result of chronic hypoxic conditions that play a role in modulating bone cell responses by inhibiting osteoblast differentiation, reducing bone formation, and reducing osteoblast matrix mineralization. 33 In a Danish population‐based cohort study, the risk of osteoporotic fractures among patients with polycythemia vera was significantly higher than in the general population. 34 Patients with chronic hypoxic status have pathophysiological responses leading to increased production of red blood cells caused by elevated serum erythropoietin levels.…”

Analysis of Bone Histomorphometry in Rat and Guinea Pig Animal Models Subject to Hypoxia

“…Bone is a highly dynamic tissue that is continuously renewed through bone remodeling. The purpose of bone remodeling is to maintain the bone biomechanical stability and bone functions [ 1 ] and evidence suggests that hypoxia is associated with alterations in bone remodeling, but the published results are contradictory [ 9 ]. Therefore, this study analyzed the changes in the bones of rat and guinea pig models who were subjected to hypoxia.…”

“…Hypoxia has been associated with the inhibition of osteoblast differentiation and maturation mainly due to the alteration of the Runx2, Sox9, Wnt, and PI3K/Akt signaling pathways. In addition, under hypoxic conditions, osteoclastogenesis and osteoclast activity could be increased, mainly through a NF-kB pathway activation and the activation of pro-resorptive genes expression [ 9 ]. Contradictory results have also been reported in clinical studies.…”

“…It seems clear that hypoxia modifies bone remodeling, but the published results are not uniform and are sometimes contradictory [ 9 ]. In this scenario, the aim of this study was to characterize the changes in bone mass subject to various hypoxic conditions for a better understanding of the bone’s response to hypoxia and its possible clinical consequences on the bone metabolism.…”

Thioredoxin-interacting protein: A new therapeutic target in bone metabolism disorders?

“…Conversely, bone remodeling maintains the stability of bone biomechanics, an important physiological bone renewal process, and includes the quiescent, activation, resorption, formation, and mineralization stages ( 3 ). Bone renewal is accomplished by a multicellular unit known as the bone remodeling unit, which includes four types of cells—bone lining cells, osteocytes, osteoclasts (OCs), and osteoblasts (OBs) ( 4 ). Bone development and growth involve chondrocytes (CCs), which do not function in isolation but are rather coordinated in the bone microenvironment ( 5 ).…”