CCN3 (NOV) Drives Degradative Changes in Aging Articular Cartilage

Aging is a major risk factor of osteoarthritis, which is characterized by the degeneration of articular cartilage. CCN3, a member of the CCN family, is expressed in cartilage and has various physiological functions during chondrocyte development, differentiation, and regeneration. Here, we examine the role of CCN3 in cartilage maintenance. During aging, the expression of Ccn3 mRNA in mouse primary chondrocytes from knee cartilage increased and showed a positive correlation with p21 and p53 mRNA. Increased accumulation of CCN3 protein was confirmed. To analyze the effects of CCN3 in vitro, either primary cultured human articular chondrocytes or rat chondrosarcoma cell line (RCS) were used. Artificial senescence induced by H2O2 caused a dose-dependent increase in Ccn3 gene and CCN3 protein expression, along with enhanced expression of p21 and p53 mRNA and proteins, as well as SA-beta gal activity. Overexpression of CCN3 also enhanced p21 promoter activity via p53. Accordingly, the addition of recombinant CCN3 protein to the culture increased the expression of p21 and p53 mRNAs. We have produced cartilage-specific CCN3-overexpressing transgenic mice, and found degradative changes in knee joints within two months. Inflammatory gene expression was found even in the rib chondrocytes of three-month-old transgenic mice. Similar results were observed in human knee articular chondrocytes from patients at both mRNA and protein levels. These results indicate that CCN3 is a new senescence marker of chondrocytes, and the overexpression of CCN3 in cartilage may in part promote chondrocyte senescence, leading to the degeneration of articular cartilage through the induction of p53 and p21

Double strand break repair by capture of retrotransposon sequences and reverse-transcribed spliced mRNA sequences in mouse zygotes

Ono, R., Ishii, M., Fujihara, Y. et al. Double strand break repair by capture of retrotransposon sequences and reverse-transcribed spliced mRNA sequences in mouse zygotes. Sci Rep 5, 12281 (2015). https://doi.org/10.1038/srep1228

Discrepancies between pathological examination and imaging analysis after primary systemic chemotherapy for breast cancer: report of two cases

Primary systemic chemotherapy (PSC) in breast cancer prolongs disease-free survival in patients who have obtained pathological complete remission (pCR). In combination with pathological examination, CT and MRI have been used to evaluate the efficacy of PSC, they generally coincide well with pathological evaluation. We here present two cases showing discrepancies between pathological examination and imaging analysis after PSC in breast cancer. We should keep such discrepancies in mind to determine the ideal treatment after PSC. An accurate method of evaluating cellular damage by PSC is needed

Duct lavage cytology for the detection of breast cancer: report of a case

Although many modalities have been established to diagnose breast cancers, it is sometimes difficult to reveal nonpalpable cases. Duct lavage cytology was originally established to reveal groups at high risk for breast cancers by detecting metaplastic ductal cells. We report here a case where duct lavage was useful for revealing a small cancer that had been undetected by repeated bloody nipple discharge and cytological examinations. Duct lavage cytology may be of use in cases where nipple discharge of unknown origin persists

Localization of nonpalpable breast cancers using VATS marking system under ultrasonographic guidance

A preoperative tumor guiding system for nonpalpable breast cancer using a VATS guiding needle (Hakko Co., Ltd., Tokyo Japan) was reported. It was easy to introduce the guiding needle into breast cancers smaller than 1cm under ultrasonographic observation. Neither bleeding nor infection was experienced. Wound management was easy and painless. This guiding system is very useful for locating and managing nonpalpable breast cancers even in outpatient settings

Measurement of Ionized Calcium as Supplementary Marker of Bone Metastasis in Breast Cancer

The serum concentrations of ionized calcium (iCa), corrected automatically for serum pH, were measured in 67 cases with breast cancer (16 positive cases and 51 negative cases for bone metastasis). The serum concentration of iCa in the cases of positive bone metastasis was significantly higher than that in the negative cases (p<0.005). As osteoclastic bone metastasis occurred frequently in breast cancer, the measurements of serum concentrations of iCa might be of help as a supplementary marker of the diagnosis of bone metastasis

A Newly Developed Instrument of Dual Photon Absorptiometry for Bone Mineral Analysis of the Lumbar Vertebra: Study in Control and Aged Females

In order to determine the quantitatively bone mass, dual photon absorptiometry instrument using a scintillation camera was newly developed, and its basic performance was described. Furthermore, with this instrument, bone mineral at 3rd lumbar vertebra was measured in 57 women (31 controls: age 29.9±6.4 yrs., and 16 seniles: age 67.7±6.6 yrs.). The aged females, compared with the young control females, showed significantly low the all parameters of bone mineral such as bone mineral content (BMC), bone mineral density and total BMC at 3rd lumbar vertebra. Thus, it was shown that assessment of bone mineral with this instrument provided a useful information in the diagnosis of osteoporosis

Scintigraphic Findings of Bone and Bone-Marrow and Determination of Bone Mineral Density Using Photon Absorptiometry in Osteopetrosis

On a 15-year-old girl with osteopetrosis, bone and bonemarrow scintigraphy were performed. Also, bone mineral density (BMD) with quantitative CT (QCT), single photon absorptiometry (SPA) and dual photon absorptiometry (DPA) were measured. On bone scintigraphy the diffusely increased skeletal uptake and relatively diminished renal uptake were noted. On the other hand, on bone marrow scintigraphy poor accumulation in central marrow and peripheral expansion were shown. BMD value by QCT and DPA (mainly trabecular bone) was markedly high, while BMD by SPA (mainly cortical bone) was within normal range. Thus, it was shown that bone and bone-marrow scintigraphy combined with BMD measurement by photon absorptiometry were useful and essential in evaluating the pathophysiology of osteosclerosis