Thursday, July 15, 2010

Thrombospondin 2

 During development, TSP2 is upregulated in the periochondrium but downregulated in the more mature periosteum so TSP2 could play a partial role in the on/off switch for increasing height.

Thrombospondin-2 Secreted by Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Promotes Chondrogenic Differentiation.

"human umbilical cord blood-derived MSCs (hUCB-MSCs) promoted differentiation of chondroprogenitor cells by paracrine action. This paracrine effect of hUCB-MSCs on chondroprogenitor cells was increased by treatment with synovial fluid (SF) obtained from osteoarthritis (OA) patients, but was decreased by SF of fracture patients, compared to that of an untreated group. To identify paracrine factors underlying the chondrogenic effect of hUCB-MSCs, the secretomes of hUCB-MSCs stimulated by OA SF or fracture SF were analyzed using a biotin label-based antibody array. Among the proteins increased in response to these 2 kinds of SF, thrombospondin-2 (TSP-2) was specifically increased in only OA SF-treated hUCB-MSCs. In order to determine the role of TSP-2, exogenous TSP-2 was added to a micromass culture of chondroprogenitor cells. TSP-2 had chondrogenic effects on chondroprogenitor cells via PKCα, ERK, p38/MAPK, and Notch signaling pathways{Knockdown of the ERK pathway seemed to enhance the chondrogenic effects whereas knocking down the other pathways decreased the chondrogenic effect of TSP2.. Knock-down of TSP-2 expression on hUCB-MSCs using small interfering RNA (siRNA) abolished the chondrogenic effects of hUCB-MSCs on chondroprogenitor cells. In parallel with in vitro analysis, the cartilage regenerating effect of hUCB-MSCs and TSP-2 was also demonstrated using a rabbit full-thickness osteochondral-defect model. hUCB-MSCs can stimulate the differentiation of locally presented endogenous chondroprogenitor cells by TSP-2, which finally leads to cartilage regeneration."

Can TSP-2 encourage the chondrodifferentiation of MSCs and not just chondroprogenitor cells?

"Chondroprogenitor cells were isolated from the limb buds of 11.5 dpc ICR mouse embryos and
maintained as micromass cultures to induce chondrogenesis."

"TSP-2 released into the synovia promotes the differentiation of endogenous chondroprogenitor cells."

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