Tag: skeletal development

Scientists Close in on the Genetic Determinants of Height

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Human height is dictated by the sealing of the growth plates at the ends of bones that harden as a child develops. Along with diet and disease, heritability has long been known to be a factor determining height. Now, researchers report in Cell Genomics that cells in these plates determine the length and shape of bones and may partly predict final stature. The study identified potential “height genes” and found that genetic changes affecting cartilage cell maturation may strongly influence adult height.

“The study is really understanding the genetics of skeleton,” says paediatric endocrinologist and senior author Nora Renthal of Boston Children’s Hospital and Harvard University. “Height is a good starting point to understand the relationship between genes, growth plates, and skeletal growth because we can measure the height of every human being.”

To pinpoint height-associated genes, the team screened 600 million mouse cartilage cells to identify genes that, when deleted, can alter cell growth and maturation. These types of cellular changes in the growth plate are known to lead to variations in human height. The search turned up 145 genes mostly linked to skeletal disorders and are crucial for growth plate maturation and bone formation.

The team then compared these genes with data from genome-wide association studies (GWAS) of human height, which located “hotspots” along the entire human genome where “height genes” are located. But these regions can contain multiple genes, making it hard for researchers to track down and study an individual target.

“That’s kind of like looking for your friend’s house, but you only know the zip code,” says Renthal. “It’s difficult.”

The comparison revealed that genes affecting cartilage cells overlap with hotspots from human height GWAS, precisely locating genes in our DNA that likely play a role in determining our stature. Renthal and her team also discovered that many of the GWAS suggested height genes led to early maturation in cartilage cells. These findings suggest that genetic changes affecting cartilage cell maturation may influence height more.

Renthal notes that studies in mouse cells may not fully translate to humans, and GWAS are observational studies that cannot fully illustrate the cause and effects of height. But her study provides a novel method to bridge the two methods and provide new insights into human genetics.

Next, the team plans to use the method to understand hormones’ effect on cartilage cells. They will also look into some of the 145 genes that have no known connection to skeletal growth. The investigation may reveal new genes and pathways that play a role in the bones.

“I see patients with skeletal dysplasia, where there isn’t any treatment because genetics made their bones grow this way,” says Renthal. “It’s my hope that the more we can understand about the biology of the growth plate, the more we would be able to intervene at earlier times in growing skeletons and the life of a kid.”

Source: MedicalXpress

Excessive Physical Activity May Impact Teens’ Leg Development

Doctor shows an X-ray of a foot
Photo by Tima Miroshnichenko on Pexels

A study published in the Journal of Orthopaedic Research showed that physical activity levels may impact adolescents’ and young adults’ leg alignment during development, as measured by magnetic resonance imaging (MRI) scans.

The study included 57 elite male soccer players compared with 34 male and 34 female controls aged 11–21 years. Outcome measures were the hip knee angle (HKA), medial proximal tibial physeal angle (MPTPhyA), lateral distal femoral physeal angle (LDFPhyA) on full leg length MRI scans, and a physical activity questionnaire score.

Using magnetic resonance imaging scans, physical activity levels were associated with the development of varsus or ‘knock knees’, an abnormal leg alignment, which may represent a physiological adaptation to load where the shin bone meets the knee.

“Our study suggests that abnormal leg alignment, a risk factor for future injury and osteoarthritis, develops in early adolescence due to high activity levels,” said corresponding author Scott Fernquest, DPhil, of the University of Oxford. “Modifying activity levels during this critical period of growth may prevent the development of abnormal leg alignment. We hope our findings lead to further research investigating this possibility.”

Source: Wiley

Junk Food Impacts Bone Growth in Kids

Burger and chips. Photo by Jonathan Borba on Unsplash

A new study has found that ultra-processed foods (aka junk food) impacts bone quality, showing how damaging these can be especially in younger children.

The Hebrew University study provides the first comprehensive analysis showing the manner in which such foods impact skeletal development.  

Junk foods go through many processing stages, and contain non-dietary ingredients. They are easily accessible, can be eaten without preparation and fairly cheap, and their increasing presence in diets is contributing to worldwide obesity with its associated metabolic impacts.

Children tend to like junk food. As much as 70% percent of their caloric consumption are estimated to come from ultra-processed foods. While numerous studies have reflected on the overall negative impact of junk food, few have focused on its direct developmental effects on children, particularly young children.

Studying lab rodents with skeletons in post embryonic growth stages, they found that those exposed to ultra-processed foods suffered from stunted growth and compromised bone strength. With histological examination, high levels of cartilage were found in the epiphyseal plates at the end of bones. The RNA genetic profiles of cartilage cells exposed to ultra-processed food also showed signs of impaired boned development.

In order to understand how eating habits might impact bone development, the researchers replicated this kind of food intake for the rodents. “We divided the rodents’ weekly nutritional intake—30% came from a ‘controlled’ diet, 70% from ultra-processed foods,” said Monsonego-Ornan. They found that the rodents experienced bone density moderate damage though there were fewer signs of cartilage buildup in their growth plates. “Our conclusion was that even in reduced amounts, the ultra-processed foods can have a definite negative impact on skeletal growth.”

Children and adolescents eat junk foods in great quantities, with half of American minors eating junk food daily. Monsonego-Ornan added. “When Carlos Monteiro, one of the world’s leading experts on nutrition, said that there is no such thing as a healthy ultra-processed food, he was clearly right. Even if we reduce fats, carbs nitrates and other known harmful substances, these foods still possess their damaging attributes. Every part of the body is prone to this damage and certainly those systems that remain in the critical stages of development.”

Source: Medical Xpress

Journal information: Janna Zaretsky et al. Ultra-processed food targets bone quality via endochondral ossification, Bone Research (2021). DOI: 10.1038/s41413-020-00127-9