Methods for Modulating Bone Formation and Mineralization
- 詳細技術說明
- The inventors have described methods for modulating bone formation andmineralization that can be used for the treatment of numerous bone-relateddisorders.
- *Abstract
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Bone is a dynamic tissue, and isconstantly remodeled via absorption by osteoblasts, and resorption byosteoclasts. This cyclical process goes awry in numerous bone-relateddisorders, for which, few remedies exist.
Transcription factors are importantin bone remodeling. The inventors show that the absence of a zinc fingertranscription factor called Shn3 in osteoblasts results in increased boneformation in vivo. Hence, inhibition of Shn3 provides a lucrative method ofenhancing bone formation and mineralization (and vice-versa). Similarly,altering the expression or activity of another transcription factor calledShn2, would be useful for modulating trabecular bone formation andmineralization in the diaphysis of a bone, and growth plate maturation duringendochondral ossification.
The inventors have furtheridentified positive and negative regulators of osteoblastogenesis andosteoclastogenesis. A library of compounds can be tested to identify those thatincrease or decrease bone formation and mineralization based on their abilityto modify the expression and/or activity of these regulators, or thedifferentiation of osteoblasts and osteoclasts from stem cells.
Further, the inventors havedetermined that the inhibition of ROBO signaling promotes osteoblast activity. Highlevels of protein expression were observed from 2 genes SLIT2 and SLIT3 inosteoblasts, and these ligands were shown to bind 2 receptors, ROBO1 and ROBO2.This set of ligands and receptors were shown to be involved in autocrinesignaling. The inventors showed that the inhibition of this interaction wouldbe an effective means of enhancing osteoblast differentiation resulting inenhanced bone formation and mineralization.
Potential Applications
- Treatment of bone-related disorders such as osteoporosis,progressive loss of bone density and thinning of bone tissue, bone fractures,premature fusing of 2 or more bones, osteoclastic bone destruction, criticalsize defects, calcium metabolism issues and others.
- Measurement of gene variants of the SLIT/ROBO system forclinical management of bone health.
- Research purposes: regulating the differentiation ofosteoblasts and osteoclasts to study their properties.
- *Licensing
- Brian J. Kelly, Directorbjk44@cornell.edu646-962-7045
- 其他
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·Methods for Modulating Bone Formation and Mineralization US 2008318987 A1
·Molecules Involved in Regulation of Osteoblast Activity andOsteoclast Activity, and Methods and Use Thereof US 8357637 B2
·Methods for Modulating Skeletal Remodeling and Patterning byModulating Shn2 Activity, Shn3 Activity, or Shn2 and Shn3 Activity inCombination WO 2011088163 A1
- 國家/地區
- 美國
