The following is the supplementary data related to this

The following is the supplementary data related to this article.
Acknowledgments This work was partially supported by a grant (NSC98-2311-B-003-MY3 and NSC101-2311-B-003-005) to Y. Lin from the National Science Council, Taiwan. We are grateful for the help from the Molecular Imaging Core Facility of National Taiwan Normal University and National RNAi Core Facility Platform of Academia Sinica (Taipei, Taiwan). We would like to thank Drs. Joseph Avruch and Sara Ortiz-Vega of Massachusetts General Hospital (Boston, MA, USA) for the critical reading of the manuscript and technical assistance.
Introduction MSCs are multipotent hiv protease inhibitors having the capacity to differentiate into various cell lineages, some of which generate bone, cartilage and adipose tissue (Arufe et al., 2011). Cells expressing MSC markers have been found in many tissues including the synovial membrane and cartilage tissues (Hermida-Gómez et al., 2011). In addition, osteoarthritic synovial membrane and cartilage contain more cells expressing MSC markers than do synovial membranes from healthy joints (Nagase et al., 2008). MSCs are likely to be agents of connective tissue homeostasis and repair. Lamin A and lamin C (A-type lamins, both encoded by the LMNA gene) are major components of the mammalian nuclear lamina, a complex pertinacious structure that acts as a scaffold for protein complexes that regulate nuclear structure and function (Gruenbaum et al., 2003; Prokocimer et al., 2009). Mutations in the LMNA gene play a key role in the pathogenesis of a group of diseases called laminopathies, affecting mesoderm tissues (Worman et al., 2010). One of the most studied laminopathies is Hutchinson–Gilford Progeria Syndrome (HGPS) which is due, in most of the cases, to nuclear accumulation of a permanently farnesylated, mutant form of prelamin A called progerin (PG) (Eriksson et al., 2003). HGPS is a very rare and fatal genetic disorder characterized by cellular senescence and an early onset of pathologies typical of advanced age such as atherosclerosis, myocardial infarction, stroke or OA (Hennekam, 2006). Remarkably, PG is also present in normal cells and appears to progressively accumulate during aging of non-HGPS cells (Wang et al., 2008). Besides producing structural defects in the nuclear lamina, it has also been suggested that PG may interfere with the proposed gene regulatory function of lamins, specifically the regulation of the p16/Rb pathway necessary to maintain balance between differentiation and proliferation of multipotent mesenchymal stromal or stem cells (MSCs) in tissue regeneration (Espada et al., 2008; Scaffidi and Misteli, 2008; Hernandez et al., 2010). Recently, increased accumulation of lamin A in osteoarthritis (OA) chondrocytes and cartilage (Ruiz-Romero et al., 2008; Attur et al., 2012) has been reported. OA is one of the most common skeletal disorders clinically manifested by joint pain, swelling and progressive loss of function. It is characterized by cartilage degradation, hypertrophy of the subchondral bone and osteophyte formation at the joint margins (Lamas et al., 2010). Although the underlying molecular mechanisms involved in the disease remain unknown, the etiology of OA has been considered an articular cartilage disorder induced by mechanical stress, articular injuries, involvement of inflammatory mediators and aging. Evidence suggests that cellular senescence of the chondrocyte is inherent to the OA process (Loeser, 2011). Finally, progression of the disease has been shown to be therapeutically modulated by MSCs (Mafi et al., 2011; van Buul et al., 2012). The aim of this study was to demonstrate whether lamin A deregulation in MSCs modulates the chondrogenesis process. We demonstrated that over-expression of lamin A and PG reduces the chondrogenic capacity of MSC. We also provided evidence that linked those defects to alterations in oxidative stress response through using N-acetylcysteine which protects against hypoxia produced by production of oxygen reactive species (Cillero-Pastor et al., 2008).