The specificities, influencing factors, and medical implications of bone circadian rhythms.

Physiological processes within the human body are regulated in approximately 24-h cycles known as circadian rhythms, serving to adapt to environmental changes. Bone rhythms play pivotal roles in bone development, metabolism, mineralization, and remodeling processes. Bone rhythms exhibit cell specificity, and different cells in bone display various expressions of clock genes. Multiple environmental factors, including light, feeding, exercise, and temperature, affect bone diurnal rhythms through the sympathetic nervous system and various hormones. Disruptions in bone diurnal rhythms contribute to the onset of skeletal disorders such as osteoporosis, osteoarthritis and skeletal hypoplasia. Conversely, these bone diseases can be effectively treated when aimed at the circadian clock in bone cells, including the rhythmic expressions of clock genes and drug targets. In this review, we describe the unique circadian rhythms in physiological activities of various bone cells. Then we summarize the factors synchronizing the diurnal rhythms of bone with the underlying mechanisms. Based on the review, we aim to build an overall understanding of the diurnal rhythms in bone and summarize the new preventive and therapeutic strategies for bone disorders.

Advancements of MOFs in the Field of Propane Oxidative Dehydrogenation for Propylene Production.

Compared to the currently widely used propane dehydrogenation process for propylene production, propane oxidative dehydrogenation (ODHP) offers the advantage of no thermodynamic limitations and lower energy consumption. However, a major challenge in ODHP is the occurrence of undesired over-oxidation reactions of propylene, which reduce selectivity and hinder industrialization. MOFs possess a large number of metal sites that can serve as catalytic centers, which facilitates the easier access of reactants to the catalytic centers for reaction. Additionally, their flexible framework structure allows for easier adjustment of their pores compared to metal oxides and molecular sieves, which is advantageous for the diffusion of products within the framework. This property reduces the likelihood of prolonged contact between the generated propylene and the catalytic centers, thus minimizing the possibility of over-oxidation. The research on MOF catalyzed oxidative dehydrogenation of propane (ODHP) mainly focuses on the catalytic properties of MOFs with cobalt oxygen sites and boron oxygen sites. The advantages of cobalt oxygen site MOFs include significantly reduced energy consumption, enabling catalytic reactions at temperatures of 230 °C and below, while boron oxygen site MOFs exhibit high conversion rates and selectivity, albeit requiring higher temperatures. The explicit structure of MOFs facilitates the mechanistic study of these sites, enabling further optimization of catalysts. This paper provides an overview of the recent progress in utilizing MOFs as catalysts for ODHP and explores how they promote progress in ODHP catalysis. Finally, the challenges and future prospects of MOFs in the field of ODHP reactions are discussed.

Exhaled Anesthetic Xenon Regeneration by Gas Separation Using a Metal-Organic Framework with Sorbent-Sorbate Induced-Fit.

Noble gas xenon (Xe) is an excellent anesthetic gas, but its rarity, high cost and constrained production prohibits wide use in medicine. Here, we have developed a closed-circuit anesthetic Xe recovery and reusage process with highly effective CO2-specific adsorbent CUPMOF-5 that is promising to solve the anesthetic Xe supply problem. CUPMOF-5 possesses spacious cage cavities interconnected in four directions by confinement throat apertures of ~3.4 Å, which makes it an ideal molecular sieving of CO2 from Xe, O2, N2 with the benchmark selectivity and high uptake capacity of CO2. In-situ single-crystal X-ray diffraction (SCXRD) and computational simulation solidly revealed the vital sieving role of the confined throat and the sorbent-sorbate induced-fit strengthening binding interaction to CO2. CUPMOF-5 can remove 5% CO2 even from actual moist exhaled anesthetic gases, and achieves the highest Xe recovery rate (99.8%) so far, as verified by breakthrough experiments. This endows CUPMOF-5 great potential for the on-line CO2 removal and Xe recovery from anesthetic closed-circuits.

Identification and validation of m6A RNA regulatory network in pulpitis.

BACKGROUND: N6-methyladenosine (m6A) RNA modification regulators play an important role in many human diseases, and its abnormal expression can lead to the occurrence and development of diseases. However, their significance in pulpitis remains largely unknown. Here, we sought to identify and validate the m6A RNA regulatory network in pulpitis. METHODS: Gene expression data for m6A regulators in human pulpitis and normal pulp tissues from public GEO databases were analyzed. Bioinformatics analysis including Gene ontology (GO) functional, and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses were performed by R package, and Cytoscape software was used to study the role of m6A miRNA-mRNA regulatory network in pulpitis. Quantitative real-time PCR (qRT-PCR) was performed to validate the expression of key m6A regulators in collected human pulpitis specimens. RESULTS: Differential genes between pulpitis and normal groups were found from the GEO database, and further analysis found that there were significant differences in the m6A modification-related genes ALKBH5, METTL14, METTL3, METTL16, RBM15B and YTHDF1. And their interaction relationships and hub genes were determined. The hub m6A regulator targets were enriched in immune cells differentiation, glutamatergic synapse, ephrin receptor binding and osteoclast differentiation in pulpitis. Validation by qRT-PCR showed that the expression of methylases METTL14 and METTL3 was decreased, thus these two genes may play a key role in pulpitis. CONCLUSION: Our study identified and validated the m6A RNA regulatory network in pulpitis. These findings will provide valuable resource to guide the mechanistic and therapeutic analysis of the role of key m6A modulators in pulpitis.

Effects of BMAL1 on dentinogenic differentiation of dental pulp stem cells via PI3K/Akt/mTOR pathway.

AIM: This study aimed to investigate the effect of the circadian clock gene Bmal1 on dentinogenic differentiation of dental pulp stem cells (DPSCs) under inflammatory conditions. METHODOLOGY: Dental pulp stem cells were isolated from the pulp tissue of the healthy donor and were then stimulated with different concentrations of lipopolysaccharide (LPS) to mimic inflammatory conditions. Real-time polymerase chain reaction was used to detect the gene expression of circadian clock genes Bmal1, Clock, Per1, Per2, Cry1, and Cry2. Western blot (WB) was applied to analyse the protein expression of circadian clock proteins (BMAL1, CLOCK) and dentinogenic differentiation-related proteins (DSPP, DMP1). In addition, the apoptosis and osteogenic differentiation of DPSCs were also analysed in the presence of different concentrations of LPS. RESULTS: The expression of circadian clock genes of DPSCs significantly changed in an inflammatory environment. WB analysis shows that BMAL1 is relevant to the dentinogenic differentiation of DPSCs. In low concentrations of LPS-mimicked inflammatory conditions, the expression of BMAL1 increased and promoted the dentinogenic differentiation of DPSCs. However, under high concentrations of LPS-mimicked inflammatory conditions, the expression of BMAL1 decreased and inhibited the dentinogenic differentiation of DPSCs. Moreover, the effects of BMAL1 on dentinogenic differentiation of DPSCs may be through PI3K/Akt/mTOR pathway. CONCLUSIONS: This study showed that the circadian clock gene Bmal1 affected dentinogenic differentiation of DPSCs, providing a new insight for clinical stem cell-based restorative dentinogenesis therapies.

Adsorptive removal of phenol from aqueous solution with zeolitic imidazolate framework-67.

ZIF-67(zinc-methylimidazolate framework-67), one of the zeolitic imidazolate frameworks (ZIFs), was used for the removal of phenol from aqueous solutions via adsorption and shows high adsorption capacity for phenol. The thermodynamic and kinetic adsorption behavior of ZIF-67 for phenol in water with concentration ranging from 50 to 300 ppm were investigated in a batch reactor and a ZIF-67 packed column, respectively. The effects of pH, contact time, zeta potential of the adsorbent and temperature on the adsorption behavior were evaluated, and the results demonstrated that the adsorption is primarily brought about by a specific favorable interaction (electrostatic interaction) between phenol and ZIF-67 surface. The suitability of the Langmuir adsorption model to the equilibrium data was investigated for each phenol-adsorbent system, which the results showed that the equilibrium data for all the phenol-sorbent systems fitted the Langmuir model. Thermodynamic parameters such as Gibbs free energy are calculated from the experimental data at different temperatures. The adsorbent could be perfectly regenerated at 120 °C with little loss in the adsorption ability.

The osteoclastic activity in apical distal region of molar mesial roots affects orthodontic tooth movement and root resorption in rats.

The utilization of optimal orthodontic force is crucial to prevent undesirable side effects and ensure efficient tooth movement during orthodontic treatment. However, the sensitivity of existing detection techniques is not sufficient, and the criteria for evaluating optimal force have not been yet established. Here, by employing 3D finite element analysis methodology, we found that the apical distal region (A-D region) of mesial roots is particularly sensitive to orthodontic force in rats. Tartrate-resistant acidic phosphatase (TRAP)-positive osteoclasts began accumulating in the A-D region under the force of 40 grams (g), leading to alveolar bone resorption and tooth movement. When the force reached 80 g, TRAP-positive osteoclasts started appearing on the root surface in the A-D region. Additionally, micro-computed tomography revealed a significant root resorption at 80 g. Notably, the A-D region was identified as a major contributor to whole root resorption. It was determined that 40 g is the minimum effective force for tooth movement with minimal side effects according to the analysis of tooth movement, inclination, and hyalinization. These findings suggest that the A-D region with its changes on the root surface is an important consideration and sensitive indicator when evaluating orthodontic forces for a rat model. Collectively, our investigations into this region would aid in offering valuable implications for preventing and minimizing root resorption during patients' orthodontic treatment.

Time of exercise differentially impacts bone growth in mice.

Although physical training has been shown to improve bone mass, the time of day to exercise for optimal bone growth remains uncertain. Here we show that engaging in physical activity during the early active phase, as opposed to the subsequent active or rest phase, results in a more substantial increase in bone length of male and female mice. Transcriptomic and metabolomic methodologies identify that exercise during the early active phase significantly upregulates genes associated with bone development and metabolism. Notably, oxidative phosphorylation-related genes show a rhythmic expression in the chondrification centre, with a peak at the early active phase, when more rhythmic genes in bone metabolism are expressed and bone growth is synergistically promoted by affecting oxidative phosphorylation, which is confirmed by subsequent pharmacological investigations. Finally, we construct a signalling network to predict the impact of exercise on bone growth. Collectively, our research sheds light on the intricacies of human exercise physiology, offering valuable implications for interventions.

Osteocyte ferroptosis induced by ATF3/TFR1 contributes to cortical bone loss during ageing.

Cortical bone loss is intricately associated with ageing and coincides with iron accumulation. The precise role of ferroptosis, characterized by iron overload and lipid peroxidation, in senescent osteocytes remains elusive. We found that ferroptosis was a crucial mode of osteocyte death in cortical bone during ageing. Using a single-cell transcriptome analysis, we identified activating transcription factor 3 (ATF3) as a critical driver of osteocyte ferroptosis. Elevated ATF3 expression in senescent osteocytes promotes iron uptake by upregulating transferrin receptor 1 while simultaneously inhibiting solute carrier family 7-member 11-mediated cystine import. This process leads to an iron overload and lipid peroxidation, culminating in ferroptosis. Importantly, ATF3 inhibition in aged mice effectively alleviated ferroptosis in the cortical bone and mitigated cortical bone mass loss. Taken together, our findings establish a pivotal role of ferroptosis in cortical bone loss in older adults, providing promising prevention and treatment strategies for osteoporosis and fractures.

Targeting RORα in macrophages to boost diabetic bone regeneration.

Diabetes mellitus (DM) has become a serious threat to human health. Bone regeneration deficiency and nonunion caused by DM is perceived as a worldwide epidemic, with a very high socioeconomic impact on public health. Here, we find that targeted activation of retinoic acid-related orphan receptor α (RORα) by SR1078 in the early stage of bone defect repair can significantly promote in situ bone regeneration of DM rats. Bone regeneration relies on the activation of macrophage RORα in the early bone repair, but RORα of DM rats fails to upregulation as hyperglycemic inflammatory microenvironment induced IGF1-AMPK signalling deficiency. Mechanistic investigations suggest that RORα is vital for macrophage-induced migration and proliferation of bone mesenchymal stem cells (BMSCs) via a CCL3/IL-6 depending manner. In summary, our study identifies RORα expressed in macrophages during the early stage of bone defect repair is crucial for in situ bone regeneration, and offers a novel strategy for bone regeneration therapy and fracture repair in DM patients.

Study on acoustic properties of hydrate-bearing sediments with reconstructed CO2 hydrate in different layers during CH4 hydrate mining.

Natural gas hydrate (NGH), a clean energy source with huge reserves in nature, and its safe and efficient exploitation fits perfectly with the UN Sustainable Development Goals (SDG-7). However, large-scale NGH decomposition frequently results in subsea landslides, reservoir subsidence, and collapse. In this work, in order to achieve safe and efficient exploitation of NGHs, the stability variation of different reservoir layers by depressurization/intermittent CO2/N2 injection (80:20 mol%, 50:50 mol%) was investigated using acoustic properties (P-wave velocity, elastic modulus), as well as reservoir subsidence under an overburden stress of 10 MPa. The P-wave velocity increased from 1282 m/s to 2778 m/s in the above-reservoir and from 1266 m/s to 2564 m/s in the below-reservoir, significantly increasing reservoir strength after CO2 hydrate formation. The P-wave velocity and elastic modulus in the top reconstructed reservoir were continually decreased by the shear damage of the overlying stress, while they remained stable in the bottom reconstructed reservoir during hydrate mining. However, due to superior pressure-bearing ability of the top CO2 hydrate reservoir, which was lacking in the bottom CO2 hydrate reservoir, the reservoir subsidence was relieved greatly. Despite the stiffness strength of reconstructed reservoir was ensured with CO2/N2 sweeping, the skeletal structure of CH4 hydrate reservoir was destroyed, and only the formation of CO2 hydrate could guarantee the stability of P-wave velocity and elastic modulus which was most beneficial to relieve reservoir subsidence. A large amount of CO2 was used in reservoir reconstruction and CH4 hydrate mining, which achieved the geological storage of CO2 (SDG-13). This work provided a new idea for safe and efficient NGHs mining in the future, and the application of acoustic properties served as a guide for the efficient construction of reconstructed reservoirs and offers credible technical assistance for safe exploitation of NGHs.

F. nucleatum facilitates oral squamous cell carcinoma progression via GLUT1-driven lactate production.

BACKGROUND: Tumor-resident microbiota has been documented for various cancer types. Oral squamous cell carcinoma (OSCC) is also enriched with microbiota, while the significance of microbiota in shaping the OSCC microenvironment remains elusive. METHODS: We used bioinformatics and clinical sample analysis to explore relationship between F. nucleatum and OSCC progression. Xenograft tumor model, metabolic screening and RNA sequencing were performed to elucidate mechanisms of pro-tumor role of F. nucleatum. FINDINGS: We show that a major protumorigenic bacterium, F. nucleatum, accumulates in invasive margins of OSCC tissues and drives tumor-associated macrophages (TAMs) formation. The mechanistic dissection shows that OSCC-resident F. nucleatum triggers the GalNAc-Autophagy-TBC1D5 signaling, leading to GLUT1 aggregation in the plasma membrane and the deposition of extracellular lactate. Simultaneous functional inhibition of GalNAc and GLUT1 efficiently reduces TAMs formation and restrains OSCC progression. INTERPRETATION: These findings suggest that tumor-resident microbiota affects the immunomodulatory and protumorigenic microenvironment via modulating glycolysis and extracellular lactate deposition. The targeted intervention of this process could provide a distinct clinical strategy for patients with advanced OSCC. FUNDING: This work was supported by the National Natural Science Foundation of China for Key Program Projects (82030070, to LC) and Distinguished Young Scholars (31725011, to LC), as well as Innovation Team Project of Hubei Province (2020CFA014, to LC).

Developmental growth plate cartilage formation suppressed by artificial light at night via inhibiting BMAL1-driven collagen hydroxylation.

Exposure to artificial light at night (LAN) can induce obesity, depressive disorder and osteoporosis, but the pernicious effects of excessive LAN exposure on tissue structure are poorly understood. Here, we demonstrated that artificial LAN can impair developmental growth plate cartilage extracellular matrix (ECM) formation and cause endoplasmic reticulum (ER) dilation, which in turn compromises bone formation. Excessive LAN exposure induces downregulation of the core circadian clock protein BMAL1, which leads to collagen accumulation in the ER. Further investigations suggest that BMAL1 is the direct transcriptional activator of prolyl 4-hydroxylase subunit alpha 1 (P4ha1) in chondrocytes, which orchestrates collagen prolyl hydroxylation and secretion. BMAL1 downregulation induced by LAN markedly inhibits proline hydroxylation and transport of collagen from ER to golgi, thereby inducing ER stress in chondrocytes. Restoration of BMAL1/P4HA1 signaling can effectively rescue the dysregulation of cartilage formation within the developmental growth plate induced by artificial LAN exposure. In summary, our investigations suggested that LAN is a significant risk factor in bone growth and development, and a proposed novel strategy targeting enhancement of BMAL1-mediated collagen hydroxylation could be a potential therapeutic approach to facilitate bone growth.

Enhanced formation of methane hydrate from active ice with high gas uptake.

Gas hydrates provide alternative solutions for gas storage & transportation and gas separation. However, slow formation rate of clathrate hydrate has hindered their commercial development. Here we report a form of porous ice containing an unfrozen solution layer of sodium dodecyl sulfate, here named active ice, which can significantly accelerate gas hydrate formation while generating little heat. It can be readily produced via forming gas hydrates with water containing very low dosage (0.06 wt% or 600 ppm) of surfactant like sodium dodecyl sulfate and dissociating it below the ice point, or by simply mixing ice powder or natural snow with the surfactant. We prove that the active ice can rapidly store gas with high storage capacity up to 185 Vg Vw-1 with heat release of ~18 kJ mol-1 CH4 and the active ice can be easily regenerated by depressurization below the ice point. The active ice undergoes cyclic ice-hydrate-ice phase changes during gas uptake/release, thus removing most critical drawbacks of hydrate-based technologies. Our work provides a green and economic approach to gas storage and gas separation and paves the way to industrial application of hydrate-based technologies.

Nucleation of the CO2 hydrate from three-phase contact lines.

Using molecular dynamics simulations on the microsecond time scale, we investigate the nucleation and growth mechanisms of CO(2) hydrates in a water/CO(2)/silica three-phase system. Our simulation results indicate that the CO(2) hydrate nucleates near the three-phase contact line rather than at the two-phase interfaces and then grows along the contact line to form an amorphous crystal. In the nucleation stage, the hydroxylated silica surface can be understand as a stabilizer to prolong the lifetime of adsorbed hydrate cages that interact with the silica surface by hydrogen bonding, and the adsorbed cages behave as the nucleation sites for the formation of an amorphous CO(2) hydrate. After nucleation, the nucleus grows along the three-phase contact line and prefers to develop toward the CO(2) phase as a result of the hydrophilic nature of the modified solid surface and the easy availability of CO(2) molecules. During the growth process, the population of sI cages in the formed amorphous crystal is found to increase much faster than that of sII cages, being in agreement with the fact that only the sI hydrate can be formed in nature for CO(2) molecules.

Identification of a novel immune gene panel in tongue squamous cell carcinoma.

BACKGROUND: Tongue squamous cell carcinoma (TSCC) is one of the most common oral cancers. Immune activity is significantly related to the initiation and progression of TSCC. Systemic analysis of the immunogenomic landscape and identification of crucial immune-related genes (IRGs) would help understanding of TSCC. Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) provide multiple TSCC cases for use in an integrated immunogenomic study. METHODS: Immune landscape of TSCC was depicted by expression microarray data from GSE13601 and GSE34105. Univariate Cox analysis, in combination with survival analysis, was applied to select candidate IRGs with significant survival value. Survival predicting models were constructed by multivariate Cox regression and logistic regression analysis. Unsupervised clustering analysis was used to construct an immune gene panel based on prognostic IRGs to distinguish TSCC subgroups with different prognostic outcomes. Finally, IHC staining was performed to validate the clinical value of this immune-gene panel. RESULTS: Differentially expressed IRGs were identified in two TSCC microarray datasets. Functional enrichment analysis revealed that ontology terms associated with variations in T cell function, were highly enriched. Infiltration status of activated CD8+ T cells, central memory CD4+ T cells and type 17 T helper cells, had great prognostic value for TSCC progression. Unsupervised clustering analysis was further performed to classify TSCC patients into three subgroups. CTSG, CXCL13, and VEGFA were finally combined together to form an immune-gene panel, todistinguish different TSCC subgroups. IHC staining of TSCC sections further validated the clinical efficiency of the immune-gene panel consisting of prognostic IRGs to distinguish TSCC patients. CONCLUSION: VEGFA, CXCL13, and CTSG, correlated with T cell infiltration and prognostic outcome. They were screened to form an immune-gene panel to identify TSCC subgroups with different prognostic outcomes. Clinical IHC further validated the efficacy of this immune-gene panel to evaluate aggressiveness of TSCC development.

Synthesis and characterization of naphthalene derivatives for two-component heterojunction-based ambipolar field-effect transistors complemented with copper hexadecafluorophthalocyanine (F16CuPc).

In order to develop organic semiconductor materials with good performance, herein, a series of naphthalene derivatives were designed and synthesized by a "building-blocks approach" connected through α-bond, double bond, and triple bond, respectively. Thin-film transistors were fabricated in single-component and two-component modes based on these naphthalene derivatives by combining the F16CuPc as the n-type material. The ambipolar performance was investigated by adjusting the device preparation procedure with the hole and electron mobility of up to 10-2 cm2 V-1 s-1. Furthermore, the electrical performance was also improved to 0.73 cm2 V-1 s-1 using the two-component bilayer configuration.

In-situ Raman study on kinetics behaviors of hydrated bubble in thickening.

Natural gas leakage by means of bubbles in cold seep abundantly existed on the ocean floor, causing the change of ocean ecology and the increase of atmospheric temperature. Fortunately, hydrated bubbles as a way of methane sequestration can reduce the effect on the ocean ecology and the escape of gas bubbles from the ocean floor, and are getting attention. To know the growth mode and efficiency of gas hydrate sequestration on bubble, the thickening growth kinetics of hydrated bubble was studied in present work. In-situ Raman spectroscopy was used to analyze the evolution of gas pores and mass transfer channels in the sI CH4, sI CH4-C2H6 and sII CH4-C2H6 hydrate films on the hydrated bubble by the peak area ratio of Raman spectra. Three types of Raman spectra (a-, b-, and c-type), three texture structures of film (Large gas pore; Small gas pore; No gas pore) and two hydrate thickening patterns (filling of new hydrate within large gas pores; covering growth on the original hydrate lattice) were provided in the thickening of hydrated bubble. Results showed that the thickening of the hydrated bubble was a multi-stages growth, i.e., quick growth (stage I), slow growth (stage II), and no growth (stage III). The texture structures and the type and size of gas pore in hydrated bubble were critical for the kinetics growth rate of hydrated bubble in thickening. Especially, the theory of heterogeneous growth of hydrated bubble was proposed to apply the hydrate growth at the interface of two or multi- bubbles, accelerating the efficiency of carbon sequestration as the hydrated bubble. This study will provide a better theoretical basis for understanding the behaviors and efficiency of hydrated carbon sequestration on the surface of bubbles resulting from the gas leakage in the hydrate exploitation or the natural cold seep. SYNOPSIS: Hydrated bubble strongly modulates the emission of a potent greenhouse gas from the deep sea.

Dysfunction of macrophages leads to diabetic bone regeneration deficiency.

Insufficient bone matrix formation caused by diabetic chronic inflammation can result in bone nonunion, which is perceived as a worldwide epidemic, with a substantial socioeconomic and public health burden. Macrophages in microenvironment orchestrate the inflammation and launch the process of bone remodeling and repair, but aberrant activation of macrophages can drive drastic inflammatory responses during diabetic bone regeneration. In diabetes mellitus, the proliferation of resident macrophages in bone microenvironment is limited, while enhanced myeloid differentiation of hematopoietic stem cells (HSCs) leads to increased and constant monocyte recruitment and thus macrophages shift toward the classic pro-inflammatory phenotype, which leads to the deficiency of bone regeneration. In this review, we systematically summarized the anomalous origin of macrophages under diabetic conditions. Moreover, we evaluated the deficit of pro-regeneration macrophages in the diabetic inflammatory microenvironment. Finally, we further discussed the latest developments on strategies based on targeting macrophages to promote diabetic bone regeneration. Briefly, this review aimed to provide a basis for modulating the biological functions of macrophages to accelerate bone regeneration and rescue diabetic fracture healing in the future.

Low intensity near-infrared light promotes bone regeneration via circadian clock protein cryptochrome 1.

Bone regeneration remains a great clinical challenge. Low intensity near-infrared (NIR) light showed strong potential to promote tissue regeneration, offering a promising strategy for bone defect regeneration. However, the effect and underlying mechanism of NIR on bone regeneration remain unclear. We demonstrated that bone regeneration in the rat skull defect model was significantly accelerated with low-intensity NIR stimulation. In vitro studies showed that NIR stimulation could promote the osteoblast differentiation in bone mesenchymal stem cells (BMSCs) and MC3T3-E1 cells, which was associated with increased ubiquitination of the core circadian clock protein Cryptochrome 1 (CRY1) in the nucleus. We found that the reduction of CRY1 induced by NIR light activated the bone morphogenetic protein (BMP) signaling pathways, promoting SMAD1/5/9 phosphorylation and increasing the expression levels of Runx2 and Osterix. NIR light treatment may act through sodium voltage-gated channel Scn4a, which may be a potential responder of NIR light to accelerate bone regeneration. Together, these findings suggest that low-intensity NIR light may promote in situ bone regeneration in a CRY1-dependent manner, providing a novel, efficient and non-invasive strategy to promote bone regeneration for clinical bone defects.