Abstract:Osteoporosis, a significant age-related disease, is marked by diminished
bone density and an elevated risk of fractures, representing a considerable global
health challenge. Bone marrow mesenchymal stem cells (BMSCs) are essential in
maintaining bone integrity through their differentiation into osteoblasts, which are
crucial for bone formation. Nevertheless, the aging of BMSCs diminishes their
regenerative abilities and intensifies inflammation, thereby playing a critical role in
osteoporosis pathogenesis. This review explores the intricate mechanisms of BMSC
senescence and its influence on osteoporosis, detailing cellular and molecular
markers, such as oxidative stress, the senescence-associated secretory phenotype
(SASP), and pivotal signaling pathways, including P53, PI3K/mTOR, and autophagy.
We assess current interventions aimed at reducing BMSC senescence, with an
emphasis on pharmacological methods like melatonin and antioxidants, alongside nonpharmacological
strategies, such as exercise and dietary supplementation with
omega-3 fatty acids. Furthermore, the challenges and limitations of translating these
strategies into clinical applications are addressed, highlighting the necessity for
personalized medicine to accommodate treatment outcome variability. Future research
directions should focus on emerging therapeutic targets and novel interventions, such
as gene editing technologies and advanced tissue engineering techniques. By
integrating these strategies, this review endeavors to enhance the understanding and
treatment of osteoporosis, emphasizing the critical need to target BMSC senescence
to develop effective therapies.