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Expression of Noggin and Gremlin1 and its implications in fine-tuning BMP activities in mouse cartilage tissues
Xiaodan Yu1, Hiroko Kawakami1,2, Naoyuki Tahara1,2
1Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, 55455.
Abstract:
Increasing evidence supports the idea that bone morphogenetic proteins (BMPs) regulate cartilage maintenance in the adult skeleton. The aim of this study is to obtain insight into the regulation of BMP activities in the adult skeletal system. We analyzed expression of Noggin and Gremlin1, BMP antagonists that are known to regulate embryonic skeletal development, in the adult skeletal system by Noggin-LacZ and Gremlin1-LacZ knockin reporter mouse lines. Both reporters are expressed in the adult skeleton in a largely overlapping manner with some distinct patterns. Both are detected in the articular cartilage, pubic symphysis, facet joint in the vertebrae, and intervertebral disk, suggesting that they regulate BMP activities in these tissues. In a surgically induced knee osteoarthritis model in mice, expression of Noggin mRNA was lost from the articular cartilage, which correlated with loss of BMP2/4 and pSMAD1/5/8, an indicator of active BMP signaling. Both reporters are also expressed in the sterna and rib cartilage, suggesting an extensive role of BMP antagonism in adult cartilage tissue. Moreover, Noggin-LacZ was detected in sutures in the skull and broadly in the nasal cartilage, while Gremlin1-LacZ exhibits a weaker and more restricted expression domain in the nasal cartilage. These results suggest broad regulation of BMP activities by Noggin and Gremlin1 in cartilage tissues in the adult skeleton, and that BMP signaling and its antagonism by NOGGIN play a role in osteoarthritis development. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1671-1682, 2017.
Insights
Bone morphogenetic proteins (BMPs) maintain adult cartilage. Noggin and Gremlin1, BMP antagonists, are broadly expressed in adult cartilage, with Noggin loss linked to osteoarthritis development.
Area of Science:
- Skeletal Biology
- Cartilage Research
- Developmental Biology
Background:
- Bone morphogenetic proteins (BMPs) are increasingly recognized for their role in adult cartilage maintenance.
- BMP antagonists, Noggin and Gremlin1, are crucial for embryonic skeletal development.
- Understanding BMP regulation in the adult skeleton is essential for cartilage health.
Purpose of the Study:
- To investigate the expression and regulation of BMP antagonists Noggin and Gremlin1 in the adult skeletal system.
- To determine the role of BMP antagonism in adult cartilage maintenance and osteoarthritis.
- To analyze BMP signaling pathway activity in relation to Noggin expression during osteoarthritis development.
Main Methods:
- Utilized Noggin-LacZ and Gremlin1-LacZ knockin reporter mouse lines to track antagonist expression in adult mice.
- Examined expression patterns in various adult skeletal tissues, including articular cartilage, pubic symphysis, facet joints, and intervertebral discs.
- Investigated changes in Noggin expression and BMP signaling (BMP2/4, pSMAD1/5/8) in a surgically induced knee osteoarthritis model.
Main Results:
- Noggin and Gremlin1 reporters showed overlapping yet distinct expression patterns in the adult skeleton, particularly in cartilage tissues.
- Both antagonists were detected in articular cartilage, pubic symphysis, vertebral facet joints, and intervertebral discs.
- Loss of Noggin mRNA in articular cartilage of osteoarthritic mice correlated with decreased BMP2/4 and pSMAD1/5/8 signaling.
Conclusions:
- Noggin and Gremlin1 play a significant role in regulating BMP activities across various adult cartilage tissues.
- BMP antagonism, specifically by Noggin, is implicated in the pathogenesis of osteoarthritis.
- These findings highlight the extensive involvement of BMP antagonism in adult cartilage homeostasis and disease.
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