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Growth of severely hypoplastic phalanges and metacarpals in symbrachydactyly: an experimental study in mice
Yumiko Kanauchi1, Masatoshi Takahara, Mikio Harada
1Department of Orthopaedic Surgery, Yamagata University School of Medicine, Yamagata, Japan.
Insights
Severely hypoplastic phalanges in brachypodism mice show delayed ossification and lack growth plates, indicating no potential for further growth. These findings offer insights into bone hypoplasia in symbrachydactyly.
Area of Science:
- Developmental biology
- Skeletal biology
- Genetics
Background:
- Symbrachydactyly often involves severely hypoplastic phalanges and metacarpals with delayed ossification.
- The ossification pattern and growth of these hypoplastic bones are not well understood.
Purpose of the Study:
- To investigate the ossification pattern and growth of hypoplastic phalanges in brachypodism mice, a model for symbrachydactyly bone hypoplasia.
- To clarify the developmental mechanisms underlying bone hypoplasia in symbrachydactyly.
Main Methods:
- Radiography to assess ossification progression in wild-type and brachypodism mice.
- Histological staining (Safranin O, type II collagen in situ hybridization) to visualize cartilage.
- TUNEL assay for apoptosis and TRAP staining for osteoclastic activity.
Main Results:
- Brachypodism mice exhibited delayed ossification of proximal phalanges compared to wild-type.
- Hypoplastic phalanges had small cartilage anlagen, diffuse ossification, and lacked growth plates and chondroepiphyses.
- Apoptosis and osteoclastic activity were observed in the developing phalanges of brachypodism mice.
Conclusions:
- Severely hypoplastic phalanges in brachypodism mice lack growth plates and secondary growth potential.
- These findings are relevant for understanding and potentially treating symbrachydactyly with severe bone hypoplasia.
Purpose:
Severely hypoplastic phalanges and metacarpals in symbrachydactyly are often associated with a delay or failure of primary ossification evident by radiography at birth. However, little is known about the ossification pattern and further growth of severely hypoplastic bones in symbrachydactyly. To clarify this mechanism, we observed development during ossification of the hypoplastic phalanges in brachypodism mice (which carry functional null mutations of growth differentiation factor 5 and exhibit hypoplastic phalanges) as a model of the bone hypoplasia in symbrachydactyly.
Methods:
Forelimbs of wild-type and brachypodism mice from embryonic day 16.5 to 21 days after birth were sectioned. We used radiography to examine the progression of ossification; safranin O fast green-iron hematoxylin staining and in situ hybridization for type II collagen to demonstrate cartilage; the transferase-mediated nick end-labeling assay to identify apoptosis; and tartrate-resistant acid phosphatase staining to demonstrate osteoclastic activity.
Results:
In brachypodism mice, radiography showed markedly delayed ossification of the proximal phalanges in comparison with wild-type mice. Safranin O staining and type II collagen in situ hybridization showed that the cartilage anlagen of the proximal phalanges were extremely small, with diffuse endochondral ossification throughout, resulting in lack of growth plate and chondroepiphysis formation. Apoptotic cells were present under the perichondrium on the plantar side of the proximal phalanges from day 7 after birth and had spread randomly by day 14. Diffuse osteoclastic activity was evident throughout the proximal phalanges from days 7 to 14 after birth.
Conclusions:
These results indicate that severely hypoplastic proximal phalanges in brachypodism mice, although showing an endochondral ossification pattern, lack a growth plate and have no potential for secondary growth. These findings may be relevant to the treatment of symbrachydactyly with severely hypoplastic bones, which are not evident radiographically at birth.
