Mesenchymal stem cell senescence alleviates their intrinsic and seno-suppressive paracrine properties contributing to osteoarthritis development


The cover features Figure 4 "SAMP8 mice display a spontaneous OA phenotype" from Malaise

The research team tests whether by becoming senescent, the mesenchymal stromal/stem cells, found in the synovial tissue and sub-chondral bone marrow, can contribute to OA development.

When co-cultured with OA chondrocytes, senescent MSC show also a seno-suppressive properties impairment favoring tissue degeneration.

To evaluate in vivo the effects of p16INK4a-senescent MSC on healthy cartilage, the researchers rely on the SAMP8 mouse model of accelerated senescence that develops spontaneous OA.

Figure 3. Senescence modulates MSCs extrinsic properties in vitro. (A) Experimental design of the without-contact co-culture system to assess the effect of senescent human MSCs on chondrocytes from patients with OA. (B) Expression analysis by RT-qPCR in OA chondrocytes without co-culture (black columns; control), or co-cultured with proliferating MSCs (grey columns), or with senescent MSCs (white columns) for 7 days. Data are expressed as fold change relative to control (mean ± SEM of n=5); *=p<0.05, **=p<0.01.

Dr. Jean-Marc Brondello from IRMB, Univ Montpellier, INSERM, Montpellier, France said, "Tissue homeostasis is ensured by the equilibrium between self-repair mechanisms of differentiated cells and their replacements through differentiation of tissue-specific adult stem cells."

Senescent cells are characterized by growth inhibition, functional changes, and the presence of the so-called senescence-associated secretory phenotype that includes the expression of inflammatory and trophic factors as well as tissue remodeling matrix metalloproteases.

Senescence onset can occur in proliferative, post-mitotic differentiated cells, and even in resting stem cells.

During OA progression and joint aging, the number of senescent cells detected in the articular cartilage, but also in the synovium and fat pad tissue, increased.

However, among all senescent cells present in the joint during OA and aging, it is not fully understood how senescence of the resident articular osteochondral progenitors can contribute to cartilage loss of function.

The Brondello research team concluded that senescent MSCs are observed in myelodysplasic syndrome, accumulate in the nucleus pulposus of the intervertebral degenerative disc in older patients, and senescent MSCs are found early in Hutchinson Gilford Progeria syndrome.

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Correspondence to: Jean-Marc Brondello email:

Keywords: senescence, tissue homeostasis, osteoarthritis, mesenchymal stem cell

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