cDNA array reveals mechanosensitive genes in chondrocytic cells under hydrostatic pressure

Abstract

Hydrostatic pressure (HP) has a profound effect on cartilage metabolism in normal and pathological conditions, especially in weight-bearing areas of the skeletal system. As an important component of overall load, HP has been shown to affect the synthetic capacity and well-being of chondrocytes, depending on the mode, duration and magnitude of pressure. In this study we examined the effect of continuous HP on the gene expression profile of a chondrocytic cell line (HCS-2/8) using a cDNA array containing 588 well-characterized human genes under tight transcriptional control. A total of 51 affected genes were identified, many of them not previously associated with mechanical stimuli. Among the significantly up-regulated genes were immediate-early genes, and genes involved in heat-shock response (hsp70, hsp40, hsp27), and in growth arrest (GADD45, GADD153, p21(Cip1/Waf1), tob). Markedly down-regulated genes included members of the Id family genes (dominant negative regulators of basic helix-loop-helix transcription factors), and cytoplasmic dynein light chain and apoptosis-related gene NIP3. These alterations in the expression profile induce a transient heat-shock gene response and activation of genes involved in growth arrest and cellular adaptation and/or differentiation.

Dynamic patterns of mechanical stimulation co-localise with growth and cell proliferation during morphogenesis in the avian embryonic knee joint

“…It is difficult to assess the individual effects of each of these potential stimuli due to the differences between experiments; however some trends do emerge from the data. Continuous loads or high frequency, high magnitude loads inhibits cell processes such as matrix synthesis and growth (Buschmann et al, 1995;Davisson et al, 2002;Fukuda et al, 1997;Sironen et al, 2002;Wu and Chen, 2000), while low magnitude dynamic loading stimulates matrix synthesis (Buschmann et al, 1995;Davisson et al, 2002;Fukuda et al, 1997;Wu and Chen, 2000). Reduced chondrocyte proliferation was also recorded in DMB immobilised chick growth plates (Germiller and Goldstein, 1997).…”

A Novel Role for GADD45β as a Mediator of MMP-13 Gene Expression during Chondrocyte Terminal Differentiation

“…Consistent with the persistent mineralization in the bone collar surrounding the Gadd45␤ Ϫ/Ϫ growth plate, abundant tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like cells were present in the diaphyseal collar in Gadd45␤ Ϫ/Ϫ mice. 6 In contrast to Mmp-13 knock-out mice but similar to the Gadd45␤ knock-out mice, both Col10a1 knock-out mice and transgenic mice with a dominant interference Col10a1 mutation have subtle growth plate phenotypes with compressed proliferative and hypertrophic zones and altered mineral deposition (73,74). The decreased Col10a1 expression because of GADD45␤ deficiency suggests that GADD45␤ plays a role in matrix remodeling at the late hypertrophic stage The chondrodysplasia (cho/cho) mouse, which carries a loss of function mutation in the Col11a1 gene, has wider long bones and shorter length possibly because type XI collagen influences the formation of type II collagen fibrils at early stages of chondrogenesis (75).…”

“…The decreased Col10a1 expression because of GADD45␤ deficiency suggests that GADD45␤ plays a role in matrix remodeling at the late hypertrophic stage The chondrodysplasia (cho/cho) mouse, which carries a loss of function mutation in the Col11a1 gene, has wider long bones and shorter length possibly because type XI collagen influences the formation of type II collagen fibrils at early stages of chondrogenesis (75). Other ECM proteins, 6 K. Ijiri, N. Walsh, and M. B. Goldring, unpublished data. FIGURE 8.…”

“…More recently, GADD45␤, which is induced by TGF-␤ in a SMAD-dependent manner, has been identified as a positive regulator of TGF-␤-induced apoptosis (4). Although GADD45␣ has been identified on DNA microarrays as prominently expressed genes in chondrocytes from adult articular cartilage and in chondrosarcoma or immortalized chondrocyte cell lines (5,6), a role for GADD45 family members, including GADD45␤, during cartilage development has not been reported previously.…”

Continuous flow leukapheresis induces expression of stress genes in lymphocytes: impact on microarray analyses

“…5 The "10% cutoff " separating low-risk from high-risk disease has been confirmed by others and is reflected in the new World Health Organization (WHO) classification of myeloid neoplasms that subdivides RAEB into 2 subtypes, RAEB-1 and RAEB-2, with 10% blasts as the distinction between them. 6 The ATG trial of Molldrem et al preceded the WHO classification and the recently reported British antilymphocyte globulin (ALG) trial 7 also used the older French-American-British MDS classification, so it is not clear how refractory cytopenia with multilineage dysplasia patients (RCMD-another new WHO category 6 ) will respond to ATG/ALG compared with RA patients, nor is it known whether RAEB-1 patients might fare better than RAEB-2.…”