Faculty Collaboration Database

Thyroid hormones induce features of the hypertrophic phenotype and stimulate correlates of CPPD crystal formation in articular chondrocytes. J Rheumatol 1999 Feb;26(2):395-401

Date

02/11/1999

Pubmed ID

9972975

Scopus ID

2-s2.0-0032903995 (requires institutional sign-in at Scopus site)   41 Citations

Abstract

OBJECTIVE: Articular cartilage affected by calcium pyrophosphate dihydrate (CPPD) crystal deposition contains abnormal chondrocytes with morphologic similarities to the terminally differentiated hypertrophic chondrocytes that mineralize in growth plate cartilage. These chondrocytes also elaborate high levels of extracellular inorganic pyrophosphate (PPi), an essential component of the CPPD crystal. Several factors that stimulate articular chondrocyte PPi elaboration also induce terminal differentiation in growth plate chondrocytes. We hypothesized that factors such as thyroid hormones (T3 and T4) that are potent stimulants of growth plate chondrocyte hypertrophy might also stimulate articular chondrocyte hypertrophic differentiation. We also hypothesized that like transforming growth factor-beta (TGF-beta), ascorbate, and retinoic acid, thyroid hormones would increase chondrocyte PPi elaboration.

METHODS: We determined the effects of T3, T4, and TGF-beta on markers of the hypertrophic phenotype such as alkaline phosphatase (ALPase) activity and type X collagen production; and the effects of T3 and T4 on processes implicated in CPPD crystal formation including PPi elaboration and nucleoside triphosphate pyrophosphohydrolase (NTPPPH) activity in adult porcine articular chondrocytes in culture.

RESULTS: ALPase activity increased 3-fold with T3 and T4 and 1.3-fold with TGF-beta. Type X collagen levels also increased with thyroid hormone treatment. [125I]T3 binding studies proved the existence of saturable T3 receptors on chondrocytes. Media [PPi] and cellular NTPPPH activity significantly increased in cultures treated with 1-10 nM T3 or 100-500 nM T4.

CONCLUSION: Increased PPi elaboration is an additional and previously unrecognized feature of hypertrophic differentiation in articular chondrocytes. These terminally differentiated chondrocytes may play a pathogenic role in CPPD crystal deposition disease.

Author List

Rosenthal AK, Henry LA

Author

Ann K. Rosenthal MD Associate Dean, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Alkaline Phosphatase
Animals
Binding Sites
Calcium Pyrophosphate
Cell Differentiation
Cell Size
Cells, Cultured
Chondrocalcinosis
Chondrocytes
Collagen
Diphosphates
Phenotype
Pyrophosphatases
Swine
Thymidine
Thyroxine
Transforming Growth Factor beta
Triiodothyronine
Tritium