The formation of the epiphyseal bone plate, the flat bony structure that provides strength and firmness to the growth plate cartilage, was studied in the present study by using light, confocal, and scanning electron microscopy. Results obtained evidenced that this bone tissue is generated by the replacement of the lower portion of the epiphyseal cartilage. However, this process differs considerably from the usual bone tissue formation through endochondral ossification. Osteoblasts deposit bone matrix on remnants of mineralized cartilage matrix that serve as a scaffold, but also on non-mineralized cartilage surfaces and as well as within the perivascular space. These processes occur simultaneously at sites located close to each other, so that, a core of the sheet of bone is established very quickly. Subsequently, thickening and reshaping occurs by appositional growth to generate a dense parallel-fibered bone structurally intermediate between woven and lamellar bone. All these processes occur in close relationship with a cartilage but most of the bone tissue is generated in a manner that may be considered as intramembranous-like. Overall, the findings here reported provide for the first time an accurate description of the tissues and events involved in the formation of the epiphyseal bone plate and gives insight into the complex cellular events underlying bone formation at different sites on the skeleton.

The frequent dysregulation of SRC family kinases (SFK) in multiple cancers prompted various inhibitors to be actively tested in preclinical and clinical trials. Disappointingly, dasatinib and saracatinib failed to demonstrate monotherapeutic efficacy in patients with head and neck squamous cell carcinomas (HNSCC). Deeper functional and mechanistic knowledge of the actions of these drugs is therefore needed to improve clinical outcome and to develop more efficient combinational strategies. Even though the SFK inhibitors dasatinib and saracatinib robustly blocked cell migration and invasion in HNSCC cell lines, this study unveils undesirable stem cell-promoting functions that could explain the lack of clinical efficacy in HNSCC patients. These deleterious effects were targeted by the mithramycin analog EC-8042 that efficiently eliminated cancer stem cells (CSC)-enriched tumorsphere cultures as well as tumor bulk cells and demonstrated potent antitumor activity in vivo. Furthermore, combination treatment of dasatinib with EC-8042 provided favorable complementary anti-proliferative, anti-invasive, and anti-CSC functions without any noticeable adverse interactions of both agents. These findings strongly support combinational strategies with EC-8042 for clinical testing in HNSCC patients. These data may have implications on ongoing dasatinib-based trials.

X-linked hypophosphatemia (XLH), the most common form of hereditary hypophosphatemic rickets, is caused by inactivating mutations of the phosphate-regulating endopeptidase gene (PHEX). XLH is mainly characterized by short stature, bone deformities and rickets, while in hypophosphatemia, normal or low vitamin D levels and low renal phosphate reabsorption are the principal biochemical aspects. The cause of growth impairment in patients with XLH is not completely understood yet, thus making the study of the growth plate (GP) alterations necessary. New treatment strategies targeting FGF23 have shown promising results in normalizing the growth velocity and improving the skeletal effects of XLH patients. However, further studies are necessary to evaluate how this treatment affects the GP as well as its long-term effects and the impact on adult height.

Chronic kidney disease (CKD) alters the morphology and function of the growth plate (GP) of long bones by disturbing chondrocyte maturation. GP chondrocytes were analyzed in growth-retarded young rats with CKD induced by adenine intake (AD), control rats fed ad libitum (C) or pair-fed with the AD group (PF), and CKD rats treated with growth hormone (ADGH). In order to study the alterations in the process of GP maturation, we applied a procedure recently described by our group to obtain high-quality three-dimensional images of whole chondrocytes that can be used to analyze quantitative parameters like cytoplasm density, cell volume, and shape. The final chondrocyte volume was found to be decreased in AD rats, but GH treatment was able to normalize it. The pattern of variation in the cell cytoplasm density suggests that uremia could be causing a delay to the beginning of the chondrocyte hypertrophy process. Growth hormone treatment appears to be able to compensate for this disturbance by triggering an early chondrocyte enlargement that may be mediated by Nkcc1 action, an important membrane cotransporter in the GP chondrocyte enlargement.

Background: Familial hypophosphatemic rickets are disabling conditions that negatively impact physical functioning, activities of daily living, mental health and social life. The most common cause of hypophosphatemic rickets is genetic factors, such as X-linked hypophosphatemia. The evaluation of the scientific application of familial hypophosphataemic rickets aids in understanding the research landscape, identifying opportunities for improvement, and promoting significant advancements in the understanding and treatment of this medical condition. This study aimed to characterize the worldwide scientific production of articles on familial hypophosphatemic rickets indexed in Scopus, through the analysis of publication growth rate, leading countries and journals, international collaboration networks, and predominant research keywords. Methods: An observational, descriptive, and cross-sectional study was conducted through a bibliometric analysis of the worldwide scientific production of familial hypophosphatemic rickets published in journals indexed in Scopus from 2000 to 2022. To retrieve the publications, Scopus was accessed on April 4, 2023, and an advanced search was performed using a filter by title, abstract and key words, source (journals), publication year, and type of article (article and review). The search terms used were extracted from the PubMed Medical Subject Headings (MeSH) related to the disease included in the MeSH catalog. Additionally, an analysis of co-occurrence between countries and keywords was carried out with VOSviewer software. Results: This study identified 1,269 articles on familial hypophosphatemic rickets (938 articles and 331 reviews). In total, 39,548 citations were received, with an H index of 95. The majority of the articles (76.9%) were published in high-impact journals according to quartile (Q), Q1 and Q2. Scientific production has shown a growing trend in recent years. The countries with the highest scientific production are the U.S., Japan, and the United Kingdom, considering that low- and middle-income countries contribute less to international scientific production. Among 1,858 author keywords, 109 met the inclusion threshold (≥ 6 occurrences) and were grouped into five thematic clusters related to genetics, treatment, pathophysiology, complications, and clinical manifestations. Recent research trends highlight increasing focus on burosumab, quality of life, and chronic complications in familial hypophosphatemic rickets. Conclusions: Scientific production has shown sustained growth in recent years. The U.S. solidifies itself as the country leading scientific production on familial hypophosphatemic rickets.

The authors of the article would like to note an error in the acknowledgements section of this paper.