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There are now 72 government-funded ventures in Shanghai. But the report pointed out that insufficient resources are creating a bottleneck as small startups fail to emerge from hackerspaces. The solution to the problem would be to establish professional teams of angel investors, according to Zhang Yuchen, professor of business administration at Shanghai Tongji University.

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In the end, they had to turn to a supplier in Shenzhen. Abstract Background Light alteration affects the internal environment and metabolic homeostasis of the body through circadian rhythm disorders CRD. CRD is one of the factors that induce and accelerate osteoarthritis OA. Therefore, the aim of this study was to evaluate the effects of continuous dark-light DL cycle on joint inflammation, bone structure, and metabolism in normal and OA Sprague-Dawley SD rats. The pathological changes and inflammatory reactions of the cartilage and synovium of the knee joint in rats were evaluated by Safranin O-fast green and immunological staining.

Results DL cycle significantly inhibited body weight gain in normal and OA rats. DL cycle significantly destroyed the structure of subchondral bone in hindlimbs of OA rats and reduced trabecular bone numbers. N , osteoclast number, and mineralization could also be found. Conclusions These results suggested that DL cycle dampened the arthritis and promoted bone resorption and bone mass loss. Graphical abstract DL cycle affects bone turnover by regulating osteoclast production in osteoarthritic rats.

Introduction The circadian clock consists of a central clock and peripheral clock, and light is one of the many cues that can entrain the circadian clock [ 1 ]. The light signal is projected to the retina and passed into the suprachiasmatic nucleus SCN , the master circadian oscillator of mammals, through the retina hypothalamic tract RHT.

This causes a phase shift of the circadian rhythm, which synchronizes the body's internal circadian rhythm with the light and dark LD cycle of the external environment [ 2 ]. Changes in the pattern or intensity of light lead to a desynchronization between the sleep-wake rhythm and the circadian cycle, which can induce body metabolic disorders and diseases.

Previous studies suggested that shift work increased the risk of chronic metabolic-related diseases, such as cardiovascular disease, steatohepatitis, and type 2 diabetes [ 3 , 4 , 5 ]. Osteoarthritis OA is a common form of osteoarthrosis. Typical lesions of OA include cartilage loss, increased subchondral bone thickness, tidemark replication, and decreased subchondral trabecular bone mass [ 6 ].

The circadian rhythm, along with species, age, gender, and trauma, represent important factors in the influence of arthritis [ 7 ]. Circadian desynchronization increases the risk of OA in shift workers [ 9 ]. A recent study found that 24 h continuous light LL induces an inflammatory microenvironment in osteoarthritic joints, and even causes trabecular bone loss [ 10 ]. The environmental disruption of the circadian rhythms induces OA-like changes in mouse knee joint [ 11 ].

Additionally, an aging muscle phenotype and reduced specific force in the extensor digitorum longus muscle could be found in BMAL1 KO mice [ 14 ]. These results demonstrate the close interaction between the circadian rhythm and musculoskeletal system. Therefore, the aim of the study was to determine the effects of environmental lighting conditions on joint inflammation and bone metabolism in normal and OA rats to prevent bone mass loss and improve the prognosis of OA.

Four groups of rats 15 in each group, randomly selected were used for the experiments conducted under entrained conditions [ 15 ]. Two groups of normal sham rats and two groups of OA rats treated with anterior cruciate ligament transection ACLT [ 16 ]. And for sham rats, only the joint capsule of right knee was exposed and the ACL was not severed. Dark-light DL cycle consisted of lights on at 7 P.

All groups were sacrificed by decapitation at the end of the sixth week Fig. A LD and DL cycle protocol. B Body weight gain of rats at the end of study. C Linear regression of body weight gain and weeks in each group. D Safranin O and fast green staining for tibia growth plates of normal and OA rats. The staining with fast green and Safranin O solution was performed. Cartilage and synovial scoring criteria were observed and evaluated as previously described [ 17 , 18 ]. The length of growth plate was measured by CaseViewer 2.

The tissues were treated with secondary antibodies HRP labeled of the corresponding species of the primary antibody and incubated. The tissues were treated with the secondary antibody and DAPI solution in the dark. The number of osteoclasts per unit area was calculated using Image-Pro Plus 6.

Reconstruction was performed using Nrecon version 1. Von Kossa staining solution was immediately added to the tissue after the sections were rehydrated in alcohol and continuously subjected to ultraviolet rays. After hematoxylin staining, differentiation, and blue returning, the sections were dehydrated and stained with eosin solution following by mounting. Enzyme-linked immunosorbent assay of the serum On the last day of each week during the experiment, 0.

The absorbance of each antibody was measured at nm in a microplate reader. ELISAcalc software was used to calculate the regression equation of the standard linear curve according to the concentration and OD value, and a four-parameter logistic curve was selected as fitting model. The blots were developed using the ECL system Tanon; China , and the intensity of the gray bands was quantified using Image J software 1. Primer sequences are listed in Table 1.

Differences between more than two groups were analyzed by two-way ANOVA followed by a Tukey multiple-comparisons post hoc test or Kruskal-Wallis test with Dunn's correction. This indicates that DL cycle significantly slows down the body weight gain of rats. However, no significant difference in serum GH content was found among the four groups Additional file 1. Joint deterioration is markedly suppressed by the DL cycle Inflammatory cytokines and active substances in peripheral blood circulation in each group as well as arthropathology were assessed to investigate whether DL cycle affects the inflammatory response and cartilage degeneration in normal and OA rats.

Surprisingly, DL significantly increased the secretion of these pro-inflammatory factors in normal rats, but it inhibited them in OA rats. An evident edema and the marked absence of cationic staining asterisk of the cartilage matrix and superficial fibrillation and abrasion arrow were found in OA rats. E, F Immunohistochemical analysis in tibial cartilage. G, H Safranin O and fast green staining of synovium. S, synovium; T, tibia; F, femur; M, meniscus.

These results suggested that the DL cycle significantly reduced the systemic and intra-articular inflammatory response in OA rats but activated the systemic inflammatory response in normal rats. DL cycle disturbs bone metabolism and accelerates bone resorption in OA rats The lengths of both the femur and tibia of rats showed no statistical difference among four groups Fig.

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