Pleiotrophin Commits Human Bone Marrow Mesenchymal Stromal Cells towards Hypertrophy during Chondrogenesis

Abstract

Pleiotrophin (PTN) is a growth factor present in the extracellular matrix of the growth plate during bone development and in the callus during bone healing. Bone healing is a complicated process that recapitulates endochondral bone development and involves many cell types. Among those cells, mesenchymal stromal cells (MSC) are able to differentiate toward chondrogenic and osteoblastic lineages. We aimed to determine PTN effects on differentiation properties of human bone marrow stromal cells (hBMSC) under chondrogenic induction using histological analysis and quantitative reverse transcription polymerase chain reaction. PTN dramatically potentiated chondrogenic differentiation as indicated by a strong increase of collagen 2 protein, and cartilage-related gene expression. Moreover, PTN increased transcription of hypertrophic chondrocyte markers such as MMP13, collagen 10 and alkaline phosphatase and enhanced calcification and the content of collagen 10 protein. These effects are dependent on PTN receptors signaling and PI3 K pathway activation. These data suggest a new role of PTN in bone regeneration as an inducer of hypertrophy during chondrogenic differentiation of hBMSC.

Development of a simple procedure for the treatment of femoral head osteonecrosis with intra-osseous injection of bone marrow mesenchymal stromal cells: study of their biodistribution in the early time points after injection

“…pBMSCs and hBMSCs were cultured in alpha-modified Eagle’s medium (αMEM) (PAA, Les Mureaux, France) supplemented with 10% of foetal calf serum (FCS) (Stem Cell Technologies, Grenoble, France) and 0.5% ciprofloxacine (Bayer Pharma, Puteaux, France). The hBMSCs used in this study were positive for CD90, CD105, and CD73 and negative for CD34 and CD45 and were able to differentiate into osteogenic, adipogenic, and chondrogenic lineages (data not shown) as previously described [ 7 , 24 , 25 ].…”

The role of pleiotrophin in bone repair

“…The first category comprised the articles concerning the in vitro or in vivo expression of PTN [6,[8][9][10][11][12][13][14][15] or its receptors [8,9,[16][17][18][19][20] in cells of the bone or the cartilage tissue. The second category included the studies, which examined actions and possible mechanisms of PTN [8,[21][22][23][24][25][26][27] or its receptors [8,16,17,[28][29][30][31] actions in bone cells. The third category comprised of the studies, which investigate the macroscopic effects of altered PTN expression on bone formation and/or remodelling in animal models [8,[32][33][34][35][36][37][38][39][40] or in clinical studies [41].…”

“…During fracture healing, PTN is immunolocalised on both osteoblasts and endothelial cells in the well vascularised, newly formed woven bone [40] and recombinant human PTN has chemotactic effects on both human osteoblastic and endothelial cells [23]. A role for PTN in bone regeneration is also supported by data showing that PTN induces hypertrophy during chondrogenic differentiation of human bone marrow stem cells, as evidenced by increased expression of collagen 2 protein and increased transcription of hypertrophic chondrocyte markers, such as MMP13, collagen 10 and alkaline phosphatase and enhanced calcification and content of collagen 10 protein [26]. Additionally, our unpublished data demonstrate that PTN is expressed in chondrocytes during callus formation (Fig.…”

The Genetic Basis of Peyronie Disease: A Review

“…48 PTN/OSF-1 overexpression in postnatal bone has the dual effect of promoting differentiation of human bone marrow stromal cells to chondroblasts and inducing a higher bone mineral content. 49, 50 Intriguingly, calcification occurs in a subset of PD plaques, although why it occurs in one plaque and not another is currently unknown. The above data support differential gene expression profiles that likely result in variable predisposition to plaque calcification in some men with PD.…”