Effects of TGF‐β1 and triiodothyronine on cartilage maturation: In vitro analysis using long‐term high‐density micromass cultures of chick embryonic limb mesenchymal cells

Abstract

Endochondral ossification is initiated by differentiation of mesenchymal cells into chondrocytes, which produce a cartilaginous matrix, proliferate, mature, and undergo hypertrophy, followed by matrix calcification, and substitution of cartilage by bone. A number of hormones and growth factors have been implicated in this process. Using in vitro, long-term, high-density, micromass cultures of chick embryonic mesenchyme, that recapitulate the process of chondrogenesis, chondrocyte maturation, and hypertrophy, we have investigated the importance of a balance between proliferation and apoptosis in cartilage maturation, focusing specifically on the effects of transforming growth factor-b1 (TGF-b1) and the thyroid hormone, triiodothyronine (T3). Our results showed that TGF-b1 stimulates proliferation, by week 2 of culture, and T3 inhibits proliferation by week 3. Cell size increases in cultures treated with T3. Collagen type X is expressed in all culture, and delay in matrix deposition is seen only in the cultures treated with TGF-b1. T3 stimulates alkaline phosphatase activity, but not calcification. T3 enhances apoptosis, as seen by TUNEL staining, and internucleosomal DNA fragmentation. The results support the roles of T3 and TGF-b in cartilage maturation, i.e., TGF-b stimulates proliferation and suppresses hypertrophy, while T3 stimulates hypertrophy and apoptosis. ß

Effect of parathyroid hormone-related protein in an in vitro hypertrophy model for mesenchymal stem cell chondrogenesis

“…Upon switching on day 14 from standard chondrogenic to hypertrophic medium, TGF-β1 and dexamethasone are withdrawn and thyroid hormone is added. The latter has been shown to enhance hypertrophy both in embryonic mesenchymal cells and growth plate chondrocytes [21][22][23]. Thyroid hormone induces terminal differentiation in growth plate chondrocytes through induction of BMP-2, and BMP-2 can induce chondrocytes to undergo maturation [24].…”

A new treatment for knee osteoarthritis: Clinical evidence for the efficacy of Arthrokinex™ autologous conditioned serum

“…25 These growth factors, which include transforming growth factor beta 1 (TGF-b1), platelet-derived GF (PDGF), insulin-like GF-I (IGF-I), basic fibroblast GF (bFGF) and vascular endothelial GF (VEGF), 26,27 have been shown to stimulate chondrocyte proliferation and augment articular cartilage metabolism. [27][28][29] The purpose of this retrospective chart review analysis is to determine if Arthrokinex TM (ACS) significantly reduced pain and increased function in patients with symptomatic KOA.…”

Role and Mechanisms of Actions of Thyroid Hormone on the Skeletal Development

“…T3 stimulates clonal expansion of resting chondrocyte progenitor cells but inhibits subsequent chondrocyte proliferation, while stimulating hypertrophic differentiation (75)(76)(77)(78)(79). Accordingly, T3 induces markers of hypertrophic chondrocyte differentiation, including alkaline phosphatase and collagen X expression in primary growth-plate chondrocyte cultures, and enhances cartilage matrix mineralization (75).…”