BMC Musculoskelet Disord. 2014 Feb 25;15:56. doi: 10.1186/1471-2474-15-56.

Effects of hyperbaric oxygen on the osteogenic differentiation of mesenchymal stem cells

Lin SS, Ueng SW, Niu CC, Yuan LJ, Yang CY, Chen WJ, Lee MS, Chen JK1.

Author information

  • 1Department of Physiology, College of medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kweishan, 333 Taoyuan, Taiwan. jkc508@mail.cgu.edu.tw.



Hyperbaric oxygenation was shown to increase bone healing in a rabbit model. However, little is known about the regulatory factors and molecular mechanism involved. We hypothesized that the effect of hyperbaric oxygen (HBO) on bone formation is mediated via increases in the osteogenic differentiation of mesenchymal stem cells (MSCs) which are regulated by Wnt signaling.


The phenotypic characterization of the MSCs was analyzed by flow cytometric analysis. To investigate the effects of HBO on Wnt signaling and osteogenic differentiation of MSCs, mRNA and protein levels of Wnt3a, beta-catenin, GSK-3beta, Runx 2, as well as alkaline phosphatase activity, calcium deposition, and the intensity of von Kossa staining were analyzed after HBO treatment. To investigate the effects of HBO on Wnt processing and secretion, the expression of Wntless and vacuolar ATPases were quantified after HBO treatment.


Cells expressed MSC markers such as CD105, CD146, and STRO-1. The mRNA and protein levels of Wnt3a, β-catenin, and Runx 2 were up-regulated, while GSK-3β was down-regulated after HBO treatment. Western blot analysis showed an increased β-catenin translocation with a subsequent stimulation of the expression of target genes after HBO treatment. The above observation was confirmed by small interfering (si)RNA treatment. HBO significantly increased alkaline phosphatase activity, calcium deposition, and the intensity of von Kossa staining of osteogenically differentiated MSCs. We further showed that HBO treatment increased the expression of Wntless, a retromer trafficking protein, and vacuolar ATPases to stimulate Wnt processing and secretion, and the effect was confirmed by siRNA treatment.


HBO treatment increased osteogenic differentiation of MSCs via regulating Wnt processing, secretion, and signaling.


Undersea Hyperb Med. 2013 Jan-Feb;40(1):15-22.

Effects of ultra-early stage hyperbaric oxygenation on the hind limb bone mineral density in rats after complete spinal cord transection

Liu M1, Wu X, Tong M.

Author information

  • 1Department of Rehabilitation, Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, PR China. liumin22626@126.com



To study the effects of ultra-early stage hyperbaric oxygenation on the hind limb bone mineral density in rats after complete spinal cord transection.


55 SD rats were randomly assigned into three groups: sham-operated group (Sham); complete spinal cord transection. (CSCT) group; and hyperbaric oxygenation (HBO2) group. Three hours after surgery, the HBO2 group started receiving hyperbaric oxygen therapy. Bone mineral density (BMD) of total femur, total tibia and their subregions in vitro was measured with dual-energy X-ray absorptiometry (DEXA).


After the six-week treatment, BMD of total femur, BMD in regions1-2 at the distal femur, BMD in regions 6-7 at the proximal femur and BMD in regions 1-2 at the proximal tibia in vitro were markedly decreased in CSCT group at six weeks post-operation compared with that in the sham-operated group (p < 0.05-0.01). Also, in the HBO2 group, BMD value of total femur in vitro was significantly higher than that in CSCT group (p < 0.05).


Ultra-early stage hyperbaric oxygenation alleviates the hind limb bone loss in femur bone in rats following complete spinal cord transection.

Acta Orthop Belg. 2012 Oct;78(5):685-7.

There may be a role for hyperbaric oxygen therapy in transient osteoporosis of the hip

Mutluoglu M1, Sonmez G, Sivrioglu AK, Ay H.

Author information

  • 1Department of Underwater and Hyperbaric Medicine, GATA Haydarpasa Teaching Hospital, 34668 Uskudar, Istanbul, Turkey. drmutluoglu@gmail.com


Transient osteoporosis of the hip (TOH) is a rare clinical condition with usually an unknown aetiology and which typically develops in middle-aged men, or in women in the third trimester of their pregnancy. It is characterized by transient osteopenia and by gradually increasing pain associated with a limitation of the range of motion of the hip. Bone marrow oedema is a typical but nonspecific finding in TOH. A 33-year-old female patient presented with severe hip pain one month after delivery. Her history was unremarkable except for a Hashimoto's Disease of 8 years' duration. Magnetic resonance imaging (MRI) showed significant bone marrow oedema with increased signal intensity in the femoral head on T2-weighted images. A diagnosis of TOH was made and the patient received a total of 30 sessions of hyperbaric oxygen (HBO) at 2.4 ATA, 2 hours each, in a multiplace chamber. Over the course of HBO treatment, her pain was gradually relieved and she became asymptomatic after one month together with a complete recovery of the range of motion of the hip. MRI of the hips 10 weeks after onset of HBO therapy showed normal signal intensity on T2-weighted images.


Undersea Hyperb Med. 2004 Fall;31(3):275-9.

Transient osteoporosis associated with hyperhomocystinemia: a possible role for hyperbaric oxygen therapy

Domachevsky L1, Keynan Y, Militianu D, Goldenberg I, Adir Y.

Author information

  • 1Israel Naval Medical Institute, Israel Defense Forces Medical Corps, PO Box 8040, 31 080 Haifa, Israel.


Transient osteoporosis of the hip is considered by some to be an early stage of avascular necrosis. Hyperbaric oxygen (HBO2) therapy, which may be of benefit in the treatment of avascular necrosis, might therefore be used in the treatment of transient osteoporosis of the hip. We present a case of transient osteoporosis associated with elevated levels of homocysteine in a 33-year-old white male, who was treated by HBO2. Treatment was administered at 2.5 ATA for 90 minutes once daily, five days per week. Regular follow-up examinations in the course of the HBO2 therapy revealed improvement in the patient's complaints and the findings of the physical examination. Repeated magnetic resonance imaging (MRI) performed after 40 and 90 sessions showed decreased edema and complete resolution of the edema, respectively. Evaluation 6 months after the completion of treatment revealed complete resolution of symptoms, with a normal physical examination.