The number of extremely low birth weight infants less than 1,000 gram of the weight is increasing year by year because of the development of perinatal and neonatal care, the increase of elderly birth, and the high rate of multiple pregnancy. Extremely low birth weight infants caused by organ dysfunction often involve various complications such as pulmonary dysplasia syndrome, anemia, and patent ductus arteriosus. Therefore, a high oxygen care is required to prevent them and save their lives. However, the exposure of extreme changes of an oxygen concentration during the intensive care leads to retinopathy of prematurity (ROP). Abnormal extension of the retinal vessels to avascular area is observed in the patients with ROP. In the case of severe patients, ROP is a leading cause of visual field defect or blindness by the tractional retinal detachment. For the treatment of ROP, laser photocoagulation, scleral buckle, and vitreous surgery are often performed in the early stage. The injection of anti-vascular endothelial growth factor (VEGF) antibody to the lesional site is effective to inhibit abnormal extension of the retinal vessels. However, the surgical treatment for ROP infants has the risk of sequela of the central nervous system caused by anesthesia-induced developmental neurotoxicity. Furthermore, treatment with anti-VEGF antibody requires careful consideration for using because of the diversity of a VEGF molecule.
　The mast cell is one of the hematopoietic cells containing cytoplasmic granules that contain various kinds of cytokines, chemokines, and chondroitin sulfate proteoglycan, and these factors induce allergy and inflammation through degranulation process. Otherwise, mast cells also produce and release angiogenic factors.
　Recently, our research group has demonstrated that the mast cells are activated by oxygen stress through the transient receptor potentially ankyrin 1 sensing. Moreover, abnormal retinal angiogenesis is sprout by mast cell tryptase in murine oxygen-induced retinopathy, a model for ROP. We mainly describe the novel pathogenesis of ROP via mast cell activation.

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  Glucosamine (GlcN) has been widely used to treat osteoarthritis (OA) in humans. However, the effects of GlcN on autophagy in chondrocyte are still unknown. In this study, to elucidate the chondroprotective action of GlcN via autophagy on OA, we examined the effects of GlcN on the expression of autophagy-related genes and proteins (LC3-II, Beclin-1, ATG5 and ATG7) using a human chondrocyte cell line Hs 819.T. Hs 819.T cells were incubated in the absence or presence of GlcN. GlcN significantly increased protein level of LC3-II and mRNA expression of Beclin-1, ATG5 and ATG7. Moreover, GlcN significantly increased protein level of SIRT1.
　These observations suggest that GlcN increases the expression of SIRT1 and induces autophagy in chondrocytes, thereby exhibiting the chondroprotective action on OA.

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 Mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) are present in the somatic stem cell pool of the bone marrow. While MSCs differentiate primarily into osteoblasts, adipocytes and chondrocytes, HSCs differentiate primarily into hematopoietic cells and osteoclasts. Since somatic stem cells are present in a niche isolated from the external environment, they were conventionally considered to be less susceptible to the influence of changes in the external environment caused by aging. However, it has become clear from recent studies that changes in the bone marrow environment due to aging alter the properties of somatic stem cells in the bone marrow, thereby resulting in a decrease in bone density. In this review, we introduced the changes in the properties of somatic stem cells due to lifestyle diseases and dietary habits, in addition to aging.

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 In the present study, the effects of porcine liver hydrolysate (PLH) on in vivo plasma lipid levels and in vitro lipid metabolism, and were investigated. The effects of PLH on serum cholesterol levels were investigated by feeding high fat diet (HFD) to mice. The levels of total and LDL cholesterol were significantly lower than in the HFD group by feeding PLH. Lipid metabolisms related gene expressions in vitro were analysed by RT-PCR. PLH decreased low-density lipoprotein receptor (LDLR) expression. These evidences indicate PLH has serum cholesterol-lowering effects, owing to an increase in LDLR expression in hepatocytes.

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 Numbers of patients suffering from certain allergic disorders have been increasing worldwide. New allergens and haptens including chemicals, insects, and fruits, with different characters as standard allergens like pollen and house dust mite antigens have been reported almost every year. In advanced countries, there must be almost 30% of human subjects with not only serious allergic diseases but also seasonal or very mild allergies. Particularly, allergic diseases such as asthma, urticaria, food allergy, and atopic dermatitis may show negative influence on the quality of lives of patients as well as their families. Since serious allergic inflammation will induce mental stress, severe allergic diseases have become one of social problems. Multifocal investigation must take place to develop effective new drugs and therapies for subjects with allergic diseases. However, collecting samples from patients is sometimes difficult and insufficient for researchers. Therefore, detailed studies with animal models representing human allergic diseases is necessary. Moreover, placebo effects or nocebo effects never modify the results obtained from animal studies, indicating that researchers isolate true efficacy of tested regents without any modifications. We can evaluate new drug candidates, supplements, and functional foods by screening with animal models. In the current review, we summarize animal models for allergic disease including passive, active, genetically-modified models as well as the world famous spontaneous model for human atopic dermatitis, NC/Tnd mice, which has been analyzed and reported by us. Furthermore, another spontaneous model that lives with humans and develops quite similar diseases to humans, companion dogs, will be introduced. Our clinical research works using companion dogs suffered from allergic dermatitis, such as oral supplementation with mild phospholipids and shampoo treatment with the novel reagent will be outlined. Finally, we introduce the skin disorder quite similar to human urticaria in affected horses, expecting to bring a new insight into the comparative research for human disease with one of epoch-making animal models.

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 Hyaluronan (HA) has been utilized as a supplement. In a study that estimated the absorption of high molecular weight (MW) HA (900 kDa) from chicken comb cells labeled with ¹⁴C, over 88% of administered HA was absorbed and distributed throughout the body. However, the absorption mechanism of orally administrated HA has not been revealed. The degradation and absorption of HA in the intestine were investigated in this study. HA excretion into the feces, degradation in the intestinal tract, absorption through the large intestine, and translocation to the blood and skin were examined. HA administered orally was not detected in rat feces as intact HA. HA was degraded to oligosaccharides by cecal content, but not by artificial gastric and intestinal juice. Oligosaccharide HA passed through CaCo-2 cells and excised large intestine sacs. Furthermore, disaccharides and tetrasaccharides HA were distributed to the skin of rats following oral administration of high MW HA (300 kDa). The results of the study suggest that orally administered HA is degraded to oligosaccharides by intestine bacteria, and oligosaccharide HA is absorbed in the large intestine and is subsequently distributed throughout the tissues, including the skin.

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 Proteoglycans (PGs) are a group of molecules composed of one or more glycosaminoglycans bound to the core protein. They form the extracellular matrix together with collagen and hyaluronic acid. PG is known to have roles in lubrication and buffering of joint cartilage. With advancing osteoarthritis (OA), the joint cartilage becomes worn, resulting in inflammation and pain. Therefore, preservation of the cartilage components seems to be essential.
　Recently, salmon nasal cartilage-derived proteoglycan (SPG) was developed prompted by knowledge about the method of preparation of “Hizu Namasu (salmon nasal cartilage seasoned with vinegar)”, an item of the local cuisine of Hokkaido, Japan. SPG has been reported to have the effects of improving the skin appearance, suppressing blood glucose elevation, improving the intestinal flora, alleviating the symptoms of rheumatoid arthritis.
　The present study (a randomized placebo-controlled double-blind study) was undertaken to evaluate the effects of ingestion of SPG (10 mg/day) for 16 weeks on the markers of cartilage metabolism, i.e., type II collagen decomposition marker (C1, 2C) and type II collagen synthesis marker (PIICP), in 60 healthy subjects of both sexes experiencing discomfort in their knee joints (mean age 52.4 years, Kellgren-Lawrence grade 0-I). In analysis conducted in subjects with the Japanese Knee Osteoarthritis Measure (JKOM) ≥ 41 and the visual analogue scale (VAS) for knee pain at rest ≥ 1 mm, the SPG group showed a significant reduction of the Δ C1, 2C and a tendency towards reduction of the Δ C1, 2C/PIICP ratio after 16 weeks of ingestion of SPG as compared to the placebo group.
　The STR/Ort mouse (a model of spontaneous-onset OA) is known to develop OA with advancing age, presenting with human OA-like features, such as erosive degeneration and calcification of the joint cartilage and narrowing of the joint space. When STR/Ort mice (32 weeks, male) were orally treated with SPG (10 mg/kg) for 4 weeks and the influence on the knee joint tissue was evaluated by examination of safranin-O stained specimens at the end of the dosing period, SPG was shown to have suppressed cartilage injury and also suppressed the decrease of PG.
　These results suggest that SPG reduces decomposition of cartilage components and improves cartilage metabolism, thus having the potential to protect the joint cartilage.

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 The ingestion of collagen peptide has beneficial effects on the skin and joints. However, its effects on immunity have not yet been elucidated. In this study, the ingestion of fish-derived collagen peptide for 8 weeks significantly improved Scoring of Immunological Vigor score relative to that of the placebo(dextrin) group. On murine allergy model, Collagen-peptide ingestion suppressed allergic responses by improving the balance of Th1 and Th2 cells.

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 The effect of an S-adenosylmethionine-containing Yeast SM-10 dietary supplement on joint functions of individuals with knee joint pain was investigated in a randomized double-blind placebo-controlled clinical trial using 57 subjects with knee joint pain but without the diagnosis of osteoarthritis. Subjects were randomly assigned to the two groups and administered with either a test supplement containing 600 mg Yeast SM-10 (Yeast SM-10 group) or a placebo (placebo group) per day for 12 weeks, and joint functions were evaluated with the diagnostic tools for locomotive syndrome (the 25-question geriatric locomotive function scale, standing test and two-step test) as well as JOA (Japan Orthopaedic. Association) score.
　The results indicated that the subscales for the diagnostic tools for locomotive syndrome and JOA score were not significantly different between the placebo (n=29) and Yeast SM-10 (n=28) groups during the intervention, when all the subjects containing those with mild hip joint pain and low back pain were analyzed. Then, the subjects without or with weak hip joint pain and low back pain (visual analog scale scores of Japanese Orthopaedic Association Hip-Disease Evaluation Questionnaire JHEQ and Japan Low Back Pain Evaluation Questionnaire JLEQ <10 mm) were further analyzed. Notably, the two-step test was significantly improved in the Yeast SM-10 group (n=15) compared with the placebo group (n=8) at 12 weeks during the intervention. Similarly, the subscales of JOA score (pain on walking, pain on ascending or descending stairs and total) were improved in the Yeast SM-10 group compared with the placebo group at 12 weeks during the intervention.
　Together these observations suggest that the daily administration of a test supplement containing 600 mg Yeast SM-10 is effective for improving walking ability and QOL of healthy subjects with joint pain.

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 The effect of D-glucosamine hydrochloride (GlcN) administration on cartilage metabolism in bicycle players was investigated, based on the stratified analysis utilizing biomarkers for cartilage and bone metabolism.
　A randomized double-blind placebo-controlled clinical trial was conducted in 27 bicycle players. They were randomly assigned to the two groups and administrated with a placebo (n=13) or GlcN 1.5 g/day (n=14) for 3 months, and the effect of test supplements on cartilage metabolism was evaluated by analyzing a cartilage type II collagen degradation marker (CTX-II, corrected by urinary creatinine Cr) using urine samples collected before (0 month) and after the administration of test supplements (3 months).
　The results indicated that CTX-II levels were not significantly different between the two groups (placebo group and GlcN 1.5 g/day group) after the administration of test supplements (P>0.2). Next, the subject (n=18) with small joint loading were evaluated based on the CTX-II level (<500 ng/mmol Cr); CTX-II levels were substantially decreased in GlcN 1.5 g/day group (n=9, P=0.05) compared with a placebo group (n=9) after the administration of test supplement. Furthermore, among these subjects, the subject (n=13) with small variation of joint loading (<20 %) were evaluated, based on the level of NTx (a bone type I collagen degradation marker); CTX-II levels were significantly decreased in GlcN 1.5 g/day group (n=7, P <0.01) compared with a placebo group (n=6) after the administration of test supplement.
　These observations suggest that the daily administration of GlcN (1.5 g/day) exhibits the chondroprotective action on the subjects with small joint loading by improving cartilage metabolism via the suppression of type II collagen degradation.

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Objectives：To assess locomotor functions and supplement use in the urban-dwelling adults, physical function tests and a questionnaire survey were performed.
Subjects and methods：Subjects were dwelling adults living around our hospital. Demographic characteristics and supplement use was surveyed. Physical functions such as grip strength, 10m-gait time, 30-s chair-stand test(CS-30), standing time on one leg, Timed up & go test（TUG）were assessed. The presence of locomotive syndrome was evaluated using the Loco-check (stand-up test, 2-step test and locomo25 questionnaire).
Results：Fifty three adults (10 male and 43 female, average age 76.1 years old) participated this study. Among them, 66.7% participants had orthopedic conditions. Supplement users were found in 58.5% of them. Vitamins and calcium were frequent supplements. As for supplements for cartilage, chondroitin, collagen, hyaluronan, glucosamine were used in 5,4,3 and 3 participants, respectively.
Results of physical function tests were as follows：grip strength (male), 31.6Kg；grip strength (female), 19.3Kg；10m walking-time, 5.9 seconds；CS-30 17.1 times； standing time on one leg, 46.1 seconds and TUG, 7.0 seconds on average.
Loco-check revealed that 83% of participants were on the condition of locomotive syndrome. Supplement use did not cause differences in the results of physical function, however, the number of participants with locomotive syndrome was less in the supplement users and all participants without locomotive syndrome were supplement users.
Conclusion：In this study, physical function tests were performed in the urban-dwelling adults. It is a novel finding that supplements user has less locomotive syndrome.

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 Extracellular matrices (ECM) are abundant in articular cartilage and are composed of structural molecules such as chondroitin sulfate (CS), hyaluronic acid (HA), and collagen (COL). In recent years, purified CS and HA have been sometimes used in health foods for improving joint function. Although these molecules interact with one another and function intravitally, research on the influence of ECM complex on chondrocytes is limited. In this paper, we investigated the in vitro effect of adding chicken knee cartilage extract (CKCE) on the proliferation of chondrocytes.
Mouse pre-chondrogenic cell line, ATDC5 was cultured with CKCE or CKCE treated with either protease or chondroitinase, and the cell proliferation was evaluated by the WST-1 assay. The CS purified from shark cartilage and HA purified from cockscomb chicken were used as the control groups.
The chondrocyte proliferation was 1.5 times higher in the group with CKCE than in the group without CKCE. Additionally, protease- or chondroitinase-treated CKCE induced a similar increase in chondrocyte proliferation. Conversely, CS, HA, and their enzyme-treated products did not have any effect on ATDC5 proliferation.
These results indicate that low-molecular weight components different from HA and CS, which are protease- or chondroitinase-resistant, promotes the chondrocyte proliferation.

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