Boney remodeling is a chronic process of replacement with minimal change in the gross shape of the bone structure. Osteoblasts and osteoclasts together are referred to as bone remodeling units. They work in concert together, coordinated via paracrine signaling by the osteoblasts. The constant remodeling allows for calcium homeostasis and the repair of microscopic daily stressors. The histology slide show demonstrates bone remodeling with osteoclasts resorbing one side of a bony trabecula and osteoblasts depositing new bone on the other side.

One of these photos is of bone, the other is of cement foam. Which one is which? Yeah, we’re not that sure either.

And that’s the point, says bone researcher David Pastorino, who — at TEDxBarcelona — shared how he and a team of researchers have come up with a crazy new way to regenerate bone with a material quite similar to the foam of a cappuccino.

How? Well, doctors inject a foam cement made from calcium phosphate into the body after a big break and the foam mimics bone scaffolding so well that it tricks bone cells (osteoclasts and osteoblasts) into “eating” the material and replacing it with real bone. Magic? No, science!

Learn more here» 

Osteoclasts (shown) resorb bone over a period of weeks, and are especially active during periods of rapid remodeling (eg, after menopause). Because osteoclasts work faster than osteoblasts, the rate of bone loss may outpace the rate of bone production. During these periods, the newly produced bone is at increased risk for fracture because it is less densely mineralized, collagen has not matured, and resorption sites are temporarily unfilled.


Osteoporosis: balancing bone formation and degradation

  • from CNRS

“Most existing treatments for pathological bone loss inhibit osteoclasts (bone-destroyingcells) to limit bone degradation. However, by doing this, they also prevent bone formationsince it is stimulated by the presence of these very same osteoclast cells. Researchers from the CNRS, Inserm and the Université de Montpellier and Université Jean Monnet - Saint-Étienne1 have developed a new approach for preventing the destructive activity of osteoclasts without affecting their viability. This involves disrupting their anchorage to the bone, which has been found to be possible using a small chemical compound called C21. This innovative treatment can protect mice from bone loss associated with osteolytic diseases2 such as post-menopausal osteoporosis, rheumatoid arthritis and bone metastasis, without affecting bone formation. This research was published on 3 February 2015 in the journal Nature Communications

Bone is a highly dynamic tissue that is constantly in the process of being simultaneously destroyed and reconstructed. This dynamism is ensured by good coordination between the cells that destroy the “old” bone (osteoclasts) and those that reconstruct it (osteoblasts). In some diseases, bone degradation by osteoclasts exceeds bone formation by osteoblasts. As such, the challenge faced by researchers is to control osteoclast activity to avoid too high a rate of bone degradation leading to osteoporosis. However, osteoblast activity is stimulated by the presence of osteoclasts and, therefore, it is essential to find treatments for osteoporosis that reduce the activity of osteoclasts without affecting their viability. 

To destroy bone, osteoclasts use specific cell structures called podosomes, which are organized into rings by the actin cytoskeleton. Podosomes act like “snap fasteners” between the bone and the osteoclast by forming a kind of “suction cup” in which the bone is degraded. The researchers have shown that the exchange factor3 Dock5 activates a small enzyme called GTPase Rac, to organize the actin cytoskeleton and allow the formation of the ring of podosomes. Using different mouse models of pathological bone loss (post-menopause osteoporosis, rheumatoid arthritis and bone metastases), the scientists have discovered that administering a synthetic compound called C21, which inhibits Dock5, prevents osteoclast activity by blocking the “suction cup” effect that otherwise enables them to destroy the bone. Because the osteoclasts are still present, bone formation can still take place during treatment.”

(Source: CNRS; top image: WebMD; bottom image: Wikipedia)

Image of the Week - October 13, 2014

CIL:39060 - http://www.cellimagelibrary.org/images/39060

Description: Confocal micrograph of osteoblast cells labeled with Alexafluor 488 that stains alpha tubulin (green) and phalloidin marking the actin (purple) and DAPI highlighting the nucleus (yellow). Osteoblasts originate in bone marrow and contribute to the production of new bone. These cells build up the matrix of bone structure and as bone is continually being reabsorbed and regenerated these are very crucial cells. Osteoblasts make up bone and osteoclasts break it down.

Author: Kevin MacKenzie

LicensingAttribution-NonCommercial-NoDerivs 2.0 UK: England & Wales (CC BY-NC-ND 2.0 UK)

Fish reveal details of bone density loss during space missions
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JAXA - Japan Aerospace Exploration Agency logo.

September 24, 2015

Studies of medaka fish raised on the International Space Station shed light on how bone responds to sustained exposure to microgravity.

Spending time in space in a reduced gravity environment can have lasting effects on the body. For example, it is known that gravity plays a key role in the correct formation and maintenance of bone structure. Studies have shown that astronauts experience a significant drop in bone mineral density when they have been on space missions, but the exact molecular mechanisms responsible for this are unclear.

Now, Akira Kudo at Tokyo Institute of Technology, together with scientists across Japan, have shown that medaka fish reared on the International Space Station for 56 days experienced increased osteoclast activity – bone cells involved in the re-absorption of bone tissue - likely leading to a subsequent reduction of bone density. They also found several genes that were upregulated in the fish during the space mission.

The team generated fish with osteoclasts that emit a fluorescent signal. They sent 24 fish into space as juveniles, and monitored their development for 56 days under microgravity. The results were compared with a fish control group kept on Earth.

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Scientists at Tokyo Institute of Technology have shown how osteoclast volume and activity is enhanced in the upper and lower jaw bones of medaka fish after 56 days spent on the International Space Station. The team found subsequent reduction in bone density in the space fish compared with a control group of fish kept on Earth.

Kudo and his team found that bone mineral density in the pharyngeal bone (the jaw bone at the back of the throat) and the teeth of the fish reduced significantly, with decreased calcification by day 56 compared with the control group. This thinning of bone was accompanied by an increase in the volume and activity of osteoclasts. The team conducted whole transcriptome analysis of the fish jaws, and uncovered two strongly upregulated genes (fkbp5 and ddit4), together with 15 other mitochondria-related genes whose expression was also enhanced.

Reduced movement under microgravity also has an influence. The fish began to exhibit unusual behavior towards the latter stages of their stay in space, showing motionless at day 47.

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International Space Station (ISS) during STS-134 Mission
The findings provide valuable details of bone structure physiology and the abnormalities caused by the stress to the body at reduced gravity.


The impact of reduced gravity on bone tissues

Time spent in so-called ‘microgravity’ environments – where the force of gravity is considerably less than on Earth – can cause significant problems for the human body. Astronauts who spend a number of weeks in space have been shown to suffer from reduced bone mineral density, leading to skeletal problems. Other issues include problems with skin structure and a reduced ability to heal when wounded.

The precise molecular mechanisms responsible for loss of bone density are not yet fully understood. The current study by Kudo and his team is a first step towards uncovering the reasons why bone structure is affected. Their results show that osteoclast formation and activity in medaka fish increased after they spent more than two weeks in a microgravity environment. Osteoclasts are responsible for the re-absorption of bone tissue, resulting in demineralisation and decalcification of the skeleton.


Kudo and his team generated 312 modified fish whose osteoclasts and osteoblasts (cells responsible for bone formation) would emit two different fluorescent signals when activated. They sent 24 of the healthiest fish on a 56-day mission to the International Space Station (ISS), and retained a control group of modified fish on Earth.

The fish on the space station were filmed for the full two-month period in order to record unusual behavior stemming from time spent at reduced gravity. With help of the astronauts aboard the ISS, the team extracted genetic material from the fish at different stages of the process, alongside monitoring osteoclast/osteoblast activity. They performed X-ray analysis of the bones of the fish at day 56 to ascertain mineral density changes. Growth was also monitored, although overall growth tendencies remained the same regardless of gravity changes.

Future work

This study highlights the stress caused to bone structure (and the subsequent knock-on effects on functional ability) by microgravity. The researchers liken the situation to disuse osteoporosis on the ground. Their findings hold implications for longer space missions and the impact of microgravity on the human body.


Masahiro Chatani, Akiko Mantoku, Kazuhiro Takeyama, Dawud Abduweli, Yasutaka Sugamori, Kazuhiro Aoki, Keiichi Ohya, Hiromi Suzuki, Satoko Uchida, Toru Sakimura, Yasushi Kono, Fumiaki Tanigaki, Masaki Shirakawa, Yoshiro Takano and Akira Kudo.

Title of original paper:

Microgravity promotes osteoclast activity in medaka fish reared at the international space station: http://www.nature.com/articles/srep14172


Scientific Reports 5 (14172) (2015). DOI: 10.1038/srep14172.

For more information about Japan Aerospace Exploration Agency (JAXA) activities and missions, visit: http://global.jaxa.jp/

Images, Text, Credits: Japan Aerospace Exploration Agency (JAXA)/National Research and Development Agency/Tokyo Institute of Technology/NASA.

Greetings, Orbiter.ch
Full article

Lack of estrogen causes a decrease in osteoprotegerin.

Osteoprotegerin (OPG), also known as osteoclastogenesis inhibitory factor (OCIF), is a cytokine and a member of the tumor necrosis factor (TNF) receptor superfamily.

Osteoprotegerin inhibits the differentiation of macrophages into osteoclasts and also regulates the resorption of osteoclasts.
Mnemonic: Osteoprotegerin protects bone (By preventing macrophage differentiation into osteoclasts.)

Osteoprotegerin, a RANK homolog, works by binding to the RANK-ligand on Osteoblast/Stromal cells, thus blocking the RANK-RANK lingand interaction between Osteoblast/Stromal cells and Osteoclast precursors. This has the effect of inhibiting the differentiation of the Osteoclast Precursor into a mature Osteoclast.
Mnemonic: Osteoprotegerin ranks high in protecting bones.

So, estrogen kinda inhibits the osteoclasts which causes osteoporosis is the moral of the story?


Extra: Recombinant human osteoprotegerin specifically acts on bone, increasing bone mineral density and bone volume. Osteoprotegerin has been used experimentally to decrease bone resorption in women with postmenopausal osteoporosis and in patients with lytic bone metastases.

That’s all!