Chronic Intermittent Hypobaric Hypoxia Enhances Bone Fracture Healing

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Abstract

The effect of chronic intermittent hypobaric hypoxia (CIHH) on bone fracture healing is not elucidated. The present study aimed to investigate the role of CIHH on bone fracture healing and the mechanism. The Sprague-Dawley rats were randomly divided into the CIHH group and control group and monitored for 2, 4, or 8 weeks after femoral fracture surgery. Bone healing efficiency was significantly increased in the CIHH group as evidenced by higher high-density bone volume fractions, higher bone mineral density, higher maximum force, and higher stiffness. Histologically, the CIHH group exhibited superior bone formation, endochondral ossification, and angiogenic ability compared with the control group. The expression of HIF-1α and its downstream signaling proteins VEGF, SDF-1/CXCR4 axis were increased by the CIHH treatment. Moreover, the expression of RUNX2, osterix, and type I collagen in the callus tissues were also up-regulated in the CIHH group. In conclusion, our study demonstrated that CIHH treatment improves fracture healing, increases bone mineral density, and increases bone strength via the activation of HIF-1α and bone production-related genes.

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HIF-1α pathway: role, regulation and intervention for cancer therapy

Georgina Masoud, Wei Li (2015)

Hypoxia-inducible factor-1 (HIF-1) has been recognized as an important cancer drug target. Many recent studies have provided convincing evidences of strong correlation between elevated levels of HIF-1 and tumor metastasis, angiogenesis, poor patient prognosis as well as tumor resistance therapy. It was found that hypoxia (low O2 levels) is a common character in many types of solid tumors. As an adaptive response to hypoxic stress, hypoxic tumor cells activate several survival pathways to carry out their essential biological processes in different ways compared with normal cells. Recent advances in cancer biology at the cellular and molecular levels highlighted the HIF-1α pathway as a crucial survival pathway for which novel strategies of cancer therapy could be developed. However, targeting the HIF-1α pathway has been a challenging but promising progresses have been made in the past twenty years. This review summarizes the role and regulation of the HIF-1α in cancer, and recent therapeutic approaches targeting this important pathway.

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Fracture healing: mechanisms and interventions.

Thomas Einhorn, Louis C Gerstenfeld (2015)

Fractures are the most common large-organ, traumatic injuries to humans. The repair of bone fractures is a postnatal regenerative process that recapitulates many of the ontological events of embryonic skeletal development. Although fracture repair usually restores the damaged skeletal organ to its pre-injury cellular composition, structure and biomechanical function, about 10% of fractures will not heal normally. This article reviews the developmental progression of fracture healing at the tissue, cellular and molecular levels. Innate and adaptive immune processes are discussed as a component of the injury response, as are environmental factors, such as the extent of injury to the bone and surrounding tissue, fixation and the contribution of vascular tissues. We also present strategies for fracture treatment that have been tested in animal models and in clinical trials or case series. The biophysical and biological basis of the molecular actions of various therapeutic approaches, including recombinant human bone morphogenetic proteins and parathyroid hormone therapy, are also discussed.

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The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation.

Kazuhisa Nakashima, Xin Zhou, Gary A Kunkel … (2002)

We have identified a novel zinc finger-containing transcription factor, called Osterix (Osx), that is specifically expressed in all developing bones. In Osx null mice, no bone formation occurs. In endochondral skeletal elements of Osx null mice, mesenchymal cells, together with osteoclasts and blood vessels, invade the mineralized cartilage matrix. However, the mesenchymal cells do not deposit bone matrix. Similarly, cells in the periosteum and in the condensed mesenchyme of membranous skeletal elements cannot differentiate into osteoblasts. These cells do, however, express Runx2/Cbfa1, another transcription factor required for bone formation. In contrast, Osx is not expressed in Runx2/Cbfa1 null mice. Thus, Osx acts downstream of Runx2/Cbfa1. Because Osx null preosteoblasts express typical chondrocyte marker genes, we propose that Runx2/Cbfa1-expressing preosteoblasts are still bipotential cells.

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Author and article information

Contributors

Li Zhang: URI : https://loop.frontiersin.org/people/1028014

Zhiyong Hou: URI : https://loop.frontiersin.org/people/1109793

Journal

Journal ID (nlm-ta): Front Endocrinol (Lausanne)

Journal ID (iso-abbrev): Front Endocrinol (Lausanne)

Journal ID (publisher-id): Front. Endocrinol.

Title: Frontiers in Endocrinology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 1664-2392

Publication date (Electronic): 16 February 2021

Publication date Collection: 2020

Volume: 11

Electronic Location Identifier: 582670

Affiliations

[1] ¹ Department of Orthopaedic Surgery, Third Hospital of Hebei Medical University , Shijiazhuang, China

[2] ² Department of Orthopaedic Surgery, Hebei Provincial Hospital of Traditional Chinese Medicine, Hebei University of Chinese Medicine , Shijiazhuang, China

[3] ³ Department of Physiology, Hebei Medical University , Shijiazhuang, China

Author notes

Edited by: Jonathan H. Tobias, University of Bristol, United Kingdom

Reviewed by: Sadiq Umar, University of Illinois at Chicago, United States; Subhashis Pal, Emory University, United States

*Correspondence: Zhiyong Hou, drzyhou@ 123456gmail.com ; Liping Zhang, zhanglp616@ 123456163.com

This article was submitted to Bone Research, a section of the journal Frontiers in Endocrinology

Article

DOI: 10.3389/fendo.2020.582670

PMC ID: 7921462

PubMed ID: 33664707

SO-VID: a9f0f686-e2c4-4799-a1b3-7a480525ffc0

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

History

Date received : 21 July 2020

Date accepted : 14 December 2020

Page count

Figures: 6, Tables: 1, Equations: 0, References: 71, Pages: 11, Words: 4230

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Chronic Intermittent Hypobaric Hypoxia Enhances Bone Fracture Healing

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Journal of the ASEAN Federation of Endocrine Societies

Most cited references 71

HIF-1α pathway: role, regulation and intervention for cancer therapy

Fracture healing: mechanisms and interventions.

The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation.

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Cited by 6

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