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A mechanism for the increased risk of osteoarthritis development in postmenopausal women has been identified.

Обнаружен механизм увеличенного риска остеоартроза у женщин в постменопаузе.

While it has long been known that hormonal changes associated with menopause accelerate the development and progression of OA, a deeper understanding of the biological mechanisms underlying this relationship is crucial for developing effective treatment methods.

A study led by researchers at the Spaulding Rehabilitation Center, part of the Mass General Brigham healthcare system, provides new insights into the reasons behind such gender disparities. The research was published on January 16 in the journal Nature Aging.

“Our findings open up new avenues that may represent promising new therapeutic targets,” says senior study author Fabrisia Ambrosio, Ph.D., director of the Musculoskeletal Recovery Center at the Sean Adams Research Institute in Spaulding Rehabilitation Center. “We hope that understanding how menopause-induced changes in sex hormone levels contribute to joint degeneration will pave the way for researchers to develop new strategies to slow or prevent the progression of OA, which could improve the quality of life for millions of women worldwide.”

OA is characterized by the deterioration of cartilage tissue in the joints. Cartilage consists of two main components: the extracellular matrix (surrounding proteins that provide structural formation) and chondrocytes—a permanent cell population. In OA, the health of both of these components is compromised, hindering the smooth articulation of bones.

Aging is the most significant risk factor for developing OA, and over time, being female significantly exacerbates this risk. Currently, there are no disease-modifying treatments for OA, and interventions primarily focus on alleviating symptoms.

In the new study, researchers from Spaulding utilized a mouse model of menopause to comprehensively identify changes related to knee OA, from the molecular level to the whole organism. The observed changes aligned with those seen in humans: cartilage quality loss occurred at the onset of menopause, coinciding with clinical data.

The researchers then applied a sophisticated computational framework known as “network medicine” to better understand how protein interactions in cartilage change in OA. They found that menopause-induced loss of estrogen and progesterone contributes to the degradation of the extracellular matrix and the destruction of chondrocytes, while restoring these hormone levels to premenopausal levels protects against cartilage degradation.

This study represents the first authored work by a group of researchers, presenting new mechanisms for the onset of OA in older women and evaluating potential intervention measures. In a comment published last year in Nature Aging, Ambrosio and her colleagues highlighted the lack of reliable animal models of menopause, which they believe significantly hampers aging research and, consequently, clinical treatment recommendations.

This research helps to explain why the long-observed gender differences in the incidence of osteoarthritis may occur. As the scientists succeeded in protecting cartilage tissue from destruction in their models, they laid the groundwork for developing effective treatments for older women.