How Tendons Shape Developing Bones

[Guest guest]

How Tendons Shape Developing Bones

http://wis-wander.weizmann.ac.il/site/en/weizman.asp?pi=371 & doc_id=6072

Bones, muscles and tendons work together to provide the perfect balance between

stability and movement in the skeleton. Now, Weizmann Institute scientists show

that this partnership begins in the embryo, when the bones are still taking

shape. The study, published in a recent issue of Developmental Cell, describes a

previously unrecognized interaction between tendons and bones that drives the

development of a strong skeletal system.

`Our skeleton, with its bones, joints and muscle connections serves us so well

in our daily lives that we hardly pay attention to this extraordinary system,'

says Dr. Elazar Zelzer of the Weizmann Institute's Molecular Genetics

Department. `Although previous research has uncovered mechanisms that contribute

to the development and growth of each component of this complex and wonderfully

adaptable organ system, specific interactions between bones, muscles and tendons

that drive the assembly of the musculoskeletal system are not fully understood.'

Zelzer, research student Einat Blitz, Sergey Viukov and colleagues, were

interested in uncovering the molecular mechanisms that regulate the formation of

bone ridges – bony protuberances that provide a stable anchoring point for the

tendons that connect muscles with bones. Bone ridges are critical for the

skeleton's ability to cope with the considerable mechanical stresses exerted by

the muscles. The researchers used embryonic mouse skeletons to study a bone

ridge called the deltoid tuberosity, located on the humerus bone in the arm.

They discovered, to their surprise, that rather than being shaped by processes

within the skeleton, bone-ridge formation was directly regulated by tendons and

muscles in a two-phase procedure. First, the embryonic tendons initiated

bone-ridge formation by attaching to the skeleton. This interaction induced the

tendon cells to express a specific protein called scleraxis, which in turn, led

to the production of another protein, BMP4 – a molecule involved in the onset of

bone formation. Blocking BMP4 production in tendon cells prevented deltoid

tuberosity bone ridge formation. In the second phase, the subsequent growth and

ultimate size of the deltoid tuberosity was directly regulated by muscle

activity.

The results demonstrate that tendons play an active role in initiating bone

ridge patterning. Zelzer: `These findings provide a new perspective on the

regulation of skeletogenesis in the context of the musculoskeletal system, and

they shed light on an important mechanism that underlies the assembly of this

system.'

Dr. Elazar Zelzer's research is supported by the Y. Leon Benoziyo Institute for

Molecular Medicine; the Helen and Kimmel Institute for Stem Cell

Research; the Kirk Center for Childhood Cancer and Immunological Disorders; the

and Fela Shapell Family Center for Genetic Disorders Research; the estate

of Rubin Feryszka; the estate of Liebert; and the estate of Lela London.

Dr. Zelzer is the incumbent of the Martha S. Sagon Career Development Chair.

The Weizmann Institute of Science in Rehovot, Israel, is one of the world's

top-ranking multidisciplinary research institutions. Noted for its wide-ranging

exploration of the natural and exact sciences, the Institute is home to 2,600

scientists, students, technicians and supporting staff. Institute research

efforts include the search for new ways of fighting disease and hunger,

examining leading questions in mathematics and computer science, probing the

physics of matter and the universe, creating novel materials and developing new

strategies for protecting the environment.