Low level laser therapy promotes bone regeneration by coupling angiogenesis and osteogenesis
Bai J, Li L, Kou N, Bai Y, Zhang Y, Lu Y, Gao L, Wang F
Stem cell research & therapy · 79 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- Animal study (classified by our AI screen)
- Studied in
- People, plus animal or lab work
- Main outcome
- Mechanisms only
Who paid for it
- Funding
- Independent funding
- Government
- National Natural Science Foundation of China
- Government
- the Natural Science Foundation of China
- Government
- the Scientific Foundation of Education Department of Liaoning Province
- Grants
- National Natural Science Foundation of China (81802706); National Natural Science Foundation of China (81771032)
Based on 3 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2021-08-03 · Stem Cell Res Ther · vol. 12 · issue 1 · p. 432
- Publisher
- BioMed Central
- Cited
- 135 citations · more than 99% of similar papers · 10.0× the field average
- Impact
- Top 10% most cited in its field
- References
- 53 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Laser Applications in Dentistry and Medicine · Periodontal Regeneration and Treatments · Dental Implant Techniques and Outcomes
- Keywords
- Angiogenesis, Bone healing, Mesenchymal stem cell, Regeneration (biology), Stem cell, Chemistry, In vivo, CD31, Vascular endothelial growth factor, Bone marrow, Cell biology, Pathology, Biology, Medicine, Cancer research, Anatomy
- MeSH
- animals, mice, inbred c57bl, humans, mice, hydrogen peroxide, bone regeneration, osteogenesis, neovascularization, physiologic, hypoxia-inducible factor 1, alpha subunit, human umbilical vein endothelial cells, low-level light therapy
8 authors
From CN
- Jie BaiDalian Medical University
- Lijun LiDalian Medical University
- Ni KouDalian Medical University; Jinan Stomatological Hospital
- Yuwen BaiDalian Medical University
- Yaoyang ZhangDalian Medical University
- Yun LuDalian Medical University; Jinan Stomatological Hospital
Abstract
Background
Bone tissue engineering is a new concept bringing hope for the repair of large bone defects, which remains a major clinical challenge. The formation of vascularized bone is key for bone tissue engineering. Growth of specialized blood vessels termed type H is associated with bone formation. In vivo and in vitro studies have shown that low level laser therapy (LLLT) promotes angiogenesis, fracture healing, and osteogenic differentiation of stem cells by increasing reactive oxygen species (ROS). However, whether LLLT can couple angiogenesis and osteogenesis, and the underlying mechanisms during bone formation, remains largely unknown.
Methods
Mouse bone marrow mesenchymal stem cells (BMSCs) combined with biphasic calcium phosphate (BCP) grafts were implanted into C57BL/6 mice to evaluate the effects of LLLT on the specialized vessel subtypes and bone regeneration in vivo. Furthermore, human BMSCs and human umbilical vein endothelial cells (HUVECs) were co-cultured in vitro. The effects of LLLT on cell proliferation, angiogenesis, and osteogenesis were assessed.
Results
LLLT promoted the formation of blood vessels, collagen fibers, and bone tissue and also increased CD31hiEMCNhi-expressing type H vessels in mBMSC/BCP grafts implanted in mice. LLLT significantly increased both osteogenesis and angiogenesis, as well as related gene expression (HIF-1α, VEGF, TGF-β) of grafts in vivo and of co-cultured BMSCs/HUVECs in vitro. An increase or decrease of ROS induced by H2O2 or Vitamin C, respectively, resulted in an increase or decrease of HIF-1α, and a subsequent increase and decrease of VEGF and TGF-β in the co-culture system. The ROS accumulation induced by LLLT in the co-culture system was significantly decreased when HIF-1α was inhibited with DMBPA and was followed by decreased expression of VEGF and TGF-β.
Conclusions
LLLT enhanced vascularized bone regeneration by coupling angiogenesis and osteogenesis. ROS/HIF-1α was necessary for these effects of LLLT. LLLT triggered a ROS-dependent increase of HIF-1α, VEGF, and TGF-β and resulted in subsequent formation of type H vessels and osteogenic differentiation of mesenchymal stem cells. As ROS also was a target of HIF-1α, there may be a positive feedback loop between ROS and HIF-1α, which further amplified HIF-1α induction via the LLLT-mediated ROS increase. This study provided new insight into the effects of LLLT on vascularization and bone regeneration in bone tissue engineering.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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