Osteoarthritis (OA) notably affects postmenopausal women more than others, but the reasons behind this have remained unclear, which has slowed the development of effective treatments. One of the challenges in this research area is the absence of dependable animal models that simulate menopause. Recently, a study utilized a mouse model of menopause to identify a new mechanism for the onset of OA in older females and to explore potential treatment options.
Osteoarthritis (OA) is a condition that primarily impacts postmenopausal women. Those who suffer from it can share experiences of pain, limited movement, and a lower quality of life. While it has been known for years that hormonal shifts during menopause can hasten the development of OA, a clearer understanding of the biological mechanisms at play is essential for creating effective treatments.
Researchers from Spaulding Rehabilitation, part of the Mass General Brigham healthcare system, have released new findings that shed light on this gender-based disparity. Their study was published on January 16th in Nature Aging.
“Our results uncover new pathways that could serve as innovative therapeutic targets,” stated senior author Fabrisia Ambrosio, PhD, MPT, who directs the Discovery Center for Musculoskeletal Recovery at the Schoen Adams Research Institute at Spaulding Rehabilitation. “By understanding how changes in sex hormone levels due to menopause lead to joint damage, we aspire to help researchers devise new strategies that may slow or prevent OA progression, ultimately enhancing the quality of life for countless women around the globe.”
OA involves the breakdown of cartilage tissue in the joints, which consists of two main parts: the extracellular matrix, which provides structure, and chondrocytes, the cells found within cartilage. OA compromises the health of both components, disrupting the smooth movement between bones. Aging is the primary risk factor for OA, and being female significantly increases that risk over time. Currently, there are no treatments that modify the course of OA; available interventions mostly focus on alleviating symptoms.
In this recent study, the researchers at Spaulding utilized a mouse menopause model to thoroughly investigate changes related to knee OA, observing them from a molecular level to the level of the entire organism. The changes noted were similar to those documented in humans, with a decline in cartilage quality occurring at the onset of menopause, much like clinical observations. They employed a sophisticated approach known as ‘network medicine’ to analyze alterations in protein interactions within cartilage in OA. Their findings indicated that the loss of estrogen and progesterone during menopause contributes to the breakdown of the extracellular matrix and deterioration of chondrocytes. Conversely, restoring these hormones to levels typical before menopause helped prevent cartilage degeneration.
This study marks the first original publication from this research group, presenting both innovative mechanisms for OA onset in older females and testing possible interventions. In a commentary last year in Nature Aging, Ambrosio and colleagues pointed out the scarcity of reliable menopause animal models, which they argued significantly impeded research into aging and clinical practice guidance.
“This research offers insights into why the previously noted sex differences in OA prevalence may exist. We hope that since we managed to protect against cartilage degeneration in our models, we are setting the groundwork for developing effective treatments for older women,” remarked lead author Gabrielle Gilmer, PhD, a graduate student researcher at Spaulding Rehabilitation.
