Regulation of chondrocyte differentiation and maturation

Hickok, Noreen J.; Haas, and Andrew R.; Tuan, Rocky S.

doi:10.1002/(sici)1097-0029(19981015)43:2<174::aid-jemt9>3.0.co;2-p

Cited by 51 publications

(32 citation statements)

References 231 publications

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“…It is known that during embryonic cartilage development, mesenchymal cells condense and differentiate into chondrocytes. During the final stages of chondrocyte maturation, the chondrocytes undergo apoptosis and are replaced by the formation of bone through the action of osteoblasts (Hickok et al 1998). Our identification of these apoptotic cells indicates Fig.…”

Section: Discussionmentioning

confidence: 99%

Growth and apoptosis during larval forelimb development and adult forelimb regeneration in the newt (Notophthalmus viridescens)

2004

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Many of the genes involved in the initial development of the limb in higher vertebrates are also expressed during regeneration of the limb in urodeles such as Notophthalmus viridescens. These similarities have led researchers to conclude that the regeneration process is a recapitulation of development, and that patterning of the regenerate mimics pattern formation in development. However, the developing limb and the regenerating limb do not look similar. In developing urodele forelimbs, digits appear sequentially as outgrowths from the limb palette. In regeneration, all the digits appear at once. In this work, we address the issue of whether regeneration and development are similar by examining growth and apoptosis patterns. In contrast to higher vertebrates, forelimb development in the newt, N. viridescens, does not use interdigital apoptosis as the method of digit separation. During adult forelimb regeneration, apoptosis seems to play an important role in wound healing and again during cartilage to bone turnover in the advanced digits and radius/ulna. However, similar to forelimb development, demarcation of the digits in adult forelimb regeneration does not involve interdigital apoptosis. Outgrowth, rather than regression of the interdigital mesenchyme, leads to the individualization of forelimb digits in both newt development and regeneration.

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Section: Discussionmentioning

confidence: 99%

Growth and apoptosis during larval forelimb development and adult forelimb regeneration in the newt (Notophthalmus viridescens)

2004

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“…These processes involve an ordered progression of various cell differentiation stages, including proliferation, hypertrophic differentiation, terminal differentiation, and ultimately programmed cell death (apoptosis) (1,2). During normal development these sequential events are under the strict control of local and systematic factors such as hormones and growth factors.…”

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confidence: 83%

Annexin-mediated Ca2+ Influx Regulates Growth Plate Chondrocyte Maturation and Apoptosis

Wang

Kirsch

2003

Journal of Biological Chemistry

104

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Maturation of epiphyseal growth plate chondrocytes plays an important role in endochondral bone formation. Previously, we demonstrated that retinoic acid (RA) treatment stimulated annexin-mediated Ca 2؉ influx into growth plate chondrocytes leading to a significant increase in cytosolic Ca 2؉ , whereas K-201, a specific annexin Ca 2؉ channel blocker, inhibited this increase markedly. The present study addressed the hypothesis that annexin-mediated Ca 2؉ influx into growth plate chondrocytes is a major regulator of terminal differentiation, mineralization, and apoptosis of these cells. We found that K-201 significantly reduced up-regulation of expression of terminal differentiation marker genes, such as cbfa1, alkaline phosphatase (APase), osteocalcin, and type I collagen in RA-treated cultures. Maturation of epiphyseal growth plate chondrocytes, which plays an important role during endochondral ossification, is accompanied by major changes of chondrocyte morphology, biosynthetic activities, and energy metabolism. These processes involve an ordered progression of various cell differentiation stages, including proliferation, hypertrophic differentiation, terminal differentiation, and ultimately programmed cell death (apoptosis) (1, 2). During normal development these sequential events are under the strict control of local and systematic factors such as hormones and growth factors. If these processes, however, occur during pathological conditions, they can result in serious cartilage or bone defects. Evidence of endochondral ossification is also seen during osteophyte formation in osteoarthritic cartilage (3, 4). Terminal differentiation of growth plate chondrocytes is an essential process, which primes the cartilage skeleton for its subsequent invasion by osteoblasts and its replacement by a bone matrix. Despite the obvious importance of these terminal differentiation events still little is known about mechanisms regulating these processes.cbfa1, a member of the runt domain family of transcription factors, was originally discovered as a key transcription factor, which controls osteoblast differentiation. In cbfa1-null mice no endochondral and intramembranous bone formation occurs due to an arrest in osteoblast differentiation (5-8). Recent studies have indicated that cbfa1 also plays an important regulative role in terminal chondrocyte maturation. Transgenic mice, which overexpress cbfa1 in non-hypertrophic chondrocytes, display an acceleration of endochondral ossification. Overexpression of cbfa1 in chondrocytes of cbfa1-null mice partially rescued the abnormalities of cbfa1-null mutant mice. In particular, it rescued hypertrophic chondrocyte differentiation in the humerus and femur (9). Thus, cbfa1 seems to play dual functions in endochondral bone formation; it plays a key role in osteoblast differentiation from mesenchymal precursor cells, and it has the ability to stimulate hypertrophic and terminal chondrocyte differentiation.Chondrocyte hypertrophy and terminal differentiation are accompanied by an increase ...

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“…80,[82][83][84] In these systems, the role of BMPs and TGF-b's as chondroinductive proteins has been well established. Following this, several studies have shown that transfer of the cDNAs encoding these factors into mesenchymal progenitor cells can likewise be used to induce specific differentiation pathways, depending on culture conditions.…”

Section: Gene Transfer To Chondroprogenitor Cellsmentioning

confidence: 99%