It has previously been demonstrated that impaired angiogenesis is associated with metabolic abnormalities in bone in addition to osteoporosis (including postmenopausal osteoporosis). Enhancing vessel formation in bone is therefore a potential clinical therapy for osteoporosis. The present study conducted an in-depth investigation using desferrioxamine (DFO) in an ovariectomy (OVX)-induced osteoporotic mouse model in order to determine the time frame of alteration of bone characteristics and the therapeutic effect of DFO. It was demonstrated that OVX induced instant bone mass loss 1 week following surgery, as expected. In contrast, DFO treatment protected the mice against OVX-induced osteoporosis during the first week, however failed to achieve long-term protection at a later stage. A parallel alteration for cluster of differentiation 31/endomucin double positive vessels (type H vessels) was observed, which have previously been reported to be associated with osteogenesis. DFO administration not only partially prevented bone loss and maintained trabecular bone microarchitecture, however additionally enhanced the type H vessels during the first week post-OVX. The molecular mechanism of how DFO influences type H vessels to regulate bone metabolism needs to be further investigated. However, the findings of the present study provide preliminary evidence to support combined vascular and osseous therapies for osteoporotic patients. Pharmacotherapy may offer a novel target for improving osteoporosis by promoting type H vessel formation, which indicates potential clinical significance in the field of bone metabolism.

Hydrogen sulfide (H2S) has been recognized as the third gasotransmitter, following nitric oxide and carbon monoxide, and it exerts important biological effects in the body. Growing evidence has shown that H2S is involved in many physiological processes in the body. In recent years, much research has been carried out on the role of H2S in bone metabolism. Bone metabolic diseases have been linked to abnormal endogenous H2S functions and metabolism. It has been found that H2S plays an important role in the regulation of bone diseases such as osteoporosis and osteoarthritis. Regulation of H2S on bone metabolism has many interacting signaling pathways at the molecular level, which play an important role in bone formation and absorption. H2S releasing agents (donors) have achieved significant effects in the treatment of metabolic bone diseases such as osteoporosis and osteoarthritis. In addition, H2S donors and related drugs have been widely used as research tools in basic biomedical research and may be explored as potential therapeutic agents in the future. Donors are used to study the mechanism and function of H2S as they release H2S through different mechanisms. Although H2S releasers have biological activity, their function can be inconsistent. Additionally, donors have different H2S release capabilities, which could lead to different effects. Side effects may form with the formation of H2S; however, it is unclear whether these side effects affect the biological effects of H2S. Therefore, it is necessary to study H2S donors in detail. In this review, we summarize the current information about H2S donors related to bone metabolism diseases and discuss some mechanisms and biological applications.

No abstract

Background Accumulated evidence has suggested that hydrogen sulfide (H 2 S) has a role in bone formation and bone tissue regeneration. However, it is unknown whether the H 2 S content is associated with bone mineral density (BMD) in patients with osteopenia/osteoporosis. Material/Methods In the present study, we aimed to explore the changes of serum H 2 S in osteopenia and osteoporosis patients. We analyzed femur expression of cystathionine β synthase (CBS), cystathionine γ lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST), which are key enzymes for generating H 2 S. Results Sixteen (16%) patients had osteopenia, 9 (9%) had osteoporosis, and 75 (75%) had normal BMD. In comparison with patients with normal BMD (controls), the serum levels of H 2 S were unexpectedly increased in patients with osteopenia and osteoporosis. This increase was much higher in patients with osteoporosis than in those with osteopenia. Serum H 2 S levels were negatively correlated with femoral BMD, but not lumbar BMD. Interestingly, the expression of CBS and CSE were downregulated in femur tissues in patients with osteoporosis, whereas the expression of 3-MST remained unchanged. Serum phosphorus levels, alkaline phosphatase, hemoglobin, and triglycerides were found to be closely associated with CBS and CSE scores in femur tissues. Conclusions Serum H 2 S levels and femur CBS and CSE expression may be involved in osteoporosis pathogenesis.

The aim of the present study was to investigate the clinical application and utility of CdSe/ZnS quantum dots (QDs) in tracing RAW 264.7 macrophages. RAW 264.7 cells and QDs at various concentrations were co-cultured for 24 h, and the fluorescence intensity of the macrophages was determined at various time points. The mRNA expression levels of genes encoding inflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL)-1β] were determined, and cellular assays were performed to investigate the activation, proliferation and apoptosis of RAW 264.7 cells. The QDs were engulfed by the macrophages, and the fluorescence intensity of RAW 264.7 cells increased with increasing concentration and time. The IL-1β mRNA level increased significantly at 50 µg/ml QDs, and that of TNF-α increased significantly at 100 µg/ml QDs. Accelerated proliferation of RAW 264.7 cells was observed at 50 and 100 µg/ml QDs; however, no increase in apoptosis of RAW 264.7 cells was observed in co-culture. CdSe/ZnS QDs may be used as tracers due to the fluorescence intensity of RAW 264.7 cells increasing with increasing QD concentration and time, resulting in the activation of macrophages and significant increases in proliferation at 50 and 100 µg/ml QDs compared with in the absence of QDs. The change in QD concentration was not significantly associated with the proliferation and apoptosis of RAW 264.7 macrophages.