Scientists find ‘hidden’ hormone keeping mice mothers’ bones healthy

Subject: Sci

Sec: Health

Context:

Scientists have suspected that there is another way in which the body strengthens bones, independent of oestrogen.

Osteoporosis:

Osteoporosis is a condition in which the body’s bones become weak and brittle.
There are more than 10 million cases of osteoporosis every year in India, and it disproportionately affects ageing women more than men.
The hormone oestrogenplays a crucial role in this condition because it stimulates the growth and formation of new bone.
After menopause, the decreased function of ovaries leads to oestrogen being depleted in the body, resulting in the loss of bone mass.
Increased bone mass in postpartum lactating mothers is presence of the hormone CCN3.

A ‘secret’ path

Oestrogen plays a crucial osteoanabolic role: it stimulates the growth and formation of new bone. During breastfeeding, the body signals to suppress oestrogen production in the ovaries, diverting energy away from the reproductive system to focus on milk production. This drop in oestrogen should lead to weaker bones.
Mothers’ bones become stronger in this time to meet the high calcium demands of their babies and to make up for bone loss during pregnancy.
The researchers started with mice genetically modified to not produce a protein called oestrogen receptor alpha in the hypothalamus.
They found that specific neurons, called KISS1 neurons, used the CCN3 hormone to maintain bone mineralisation during lactation.
CCN3 belongs to the CCN family of proteins. They are involved in several biological processes, including embryonic development, tissue repair, wound healing, and cancer progression.
KISS1 neurons are located in the arcuate nucleus (ARC), a critical part of the hypothalamus that regulates metabolism, reproduction, and bone health. Scientists also know KISS1 neurons are key to regulating bone mass in females.

A dose-dependent response:

The researchers conducted a series of experiments to establish the role of CCN3 as an osteoanabolic hormone, i.e. that it is involved in making bone. When they extracted skeletal stem cells from wild-type mice and cultured the cells with the CCN3 hormone, they recorded a 200% increase in mineralisation.
In mice, CCN3 is absent during early and late pregnancy, appears within seven days after birth, and drops again as lactation decreases.
Deliberately reducing the amount of CCN3 hormone in KISS1 neurons before pregnancy didn’t affect a mouse mother’s fertility or ability to produce milk.
But when mothers with low CCN3 levels were lactating and had a low-calcium diet, they had lower bone density, which negatively affected the survival of their offspring.