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Magnetic resonance imaging detection of early experimental periostitis. Comparison of magnetic resonance imaging, computed tomography, and plain radiography with histopathologic correlation.

This study characterizes the appearance of periosteal reaction by magnetic resonance imaging (MRI), and evaluates the efficacy of MRI versus computed tomography (CT), and plain film radiography (PF) in detecting early, experimentally induced periostitis. Acute Staphylococcus aureus osteomyelitis was induced in 30 legs of 20 New Zealand white rabbits. The rabbits were then imaged with MR, contrast-unenhanced CT, and PF 4 days after infection. Histologically, periosteal elevation was present in 27 cases. Periosteal ossification was seen in 23 cases, and cellular reaction without ossification in 4 cases. Periosteal reaction was demonstrated by PF in 21 (78%) and by CT in 20 (74%) cases. Evidence of periostitis was seen by MR in all 27% (100%) cases. MR resulted in two false-positive diagnoses. Multiple concentric, alternating high and low signal arcs demonstrated by MR in 19 (70%) cases represented periosteal ossification surrounded by fibrous or granulation tissue. These findings demonstrate the ability of MR to detect periostitis despite the absence of periosteal ossification. MR was more sensitive than CT (P less than .05) or PF (P less than .05) in the detection of experimentally induced periostitis.

Acute Disease↗

Prefabrication of bone by use of a vascularized periosteal flap and bone morphogenetic protein.

The purpose of this pilot study was to prefabricate a vascularized bone graft by using a vascularized periosteal flap containing osteoprogenitor cells, a structural matrix, and recombinant human bone morphogenetic protein-2 (rhBMP-2). In a rat model, a periosteal flap vascularized by the saphenous artery and vein was dissected off the medial surface of the tibia. This flap consisted of three layers-periosteum, muscle, and fascia-and was tubed on itself to form a watertight chamber that was then transferred on its vascular pedicle to the groin. A total of 78 vascularized periosteal chambers were constructed in 39 animals and divided into 10 groups. In group 1, the periosteal chamber was left empty. Groups 2, 3, and 4 consisted of the periosteal flap and rhBMP-2, but in group 3, the proximal vascular pedicle was ligated, and in group 4, the flap was harvested without the periosteal layer and turned inside out. Groups 5 through 10 consisted of the vascularized periosteal flap containing several different structural matrices (calcium alginate spheres, polylactic acid, or demineralized bone matrix) with or without rhBMP-2. Animals were killed at 2, 4, or 8 weeks in each group. The presence and density of any new bone formation was evaluated both radiologically and histologically. Significant bone formation was seen only in those periosteal flaps containing rhBMP-2 and either the calcium alginate or polylactic acid matrix. New bone formation increased both radiologically and histologically from 2 weeks to 8 weeks only in the periosteal flaps containing the polylactic acid matrix and rhBMP-2. This preliminary study therefore suggests that four factors-blood supply, osteoprogenitor cells in the periosteal layer, a biodegradable matrix, and rhBMP-2-are required for optimal prefabrication of a vascularized bone graft.

Alginates↗

Prefabrication of periosteal graft alone or with oxidised cellulose: an experimental study.

The purpose of this study was to evaluate the feasibility of prefabrication of periosteal grafts, alone or with oxidised cellulose (surgicel), which was an osteoinductive material using femoral vasculature. Fifteen white New Zealand rabbits were used in both femoral regions (30 grafts), and randomly divided into three groups including five rabbits (10 grafts): the control group, the periosteal graft group, and the periosteal graft+surgicel group. A periosteal graft, 30 x 40 mm in size, was obtained from the calvarium of each rabbit. The periosteal graft taken was divided into two equal parts, 20 x 30 mm. All these periosteal grafts were sutured in the shape of tube. In all rabbits, femoral vasculature and periosteal tube was Included in a silicone tube. Additionally, in the control group, femoral vasculature was cut above and below the silicone tube, whereas in the periosteal graft+surgicel group, surgicel was added to the periosteal graft. The results were evaluated macroscopically and histopathologically in the second (two rabbits for each group - 4 grafts) and fourth week (3 rabbits for each group - 6 grafts). In the second week, In all three groups, while no osteoid tissue that indicated osteogenesis developed, it was seen that inflammation and increased vascularity occurred. Surgicel was observed to be absorbed in the periosteal graft+surgicel group. In the fourth week, fibrotic tissue was developed whereas inflammatory tissue disappeared; any osteoid tissue or lamellar bone was not accompanied in all three groups. In conclusion, we do not believe that periosteum was able to survive as a graft, and we found that neovascularization occurred too slowly to preserve the bone forming qualities of the periosteum. We suggested that it could not be prefabricated, being taken away from its donor site although surgicel was used as a stimulating material.

Animals↗

The frequency and diagnostic significance of periostitis in chondroblastoma.

A study was performed to determine the frequency of periosteal reaction associated with chondroblastoma, to investigate the underlying pathophysiology of the periosteal reaction, and to postulate the clinical importance of this radiographic observation. Two hundred fourteen histologically proved chondroblastomas were reviewed and observed for the presence or absence of periosteal reaction and for radiographic changes that might explain the cause of the periosteal reaction. A similar review was performed on 30 other epiphyseally centered lesions of various causes. A distinctive thick, solid periosteal reaction distal to the chondroblastoma was present in 47% of all chondroblastomas and 57% of chondroblastomas present in long bones (excluding the greater trochanter). No periosteal reaction was observed in any of the 30 epiphyseally centered lesions of other causes. When available for observation, plain films showed inflammatory changes in the joint surrounding the chondroblastoma, bone scintigraphy showed tracer uptake similar to that observed in inflammatory lesions and aggressive neoplasms, and MR images showed change in the marrow surrounding the chondroblastoma consistent with edema. This suggests an inflammatory reaction to the chondroblastoma, rather than mechanical stress across a weakened epiphysis, as the cause of the periostitis. We conclude that frequently the chondroblastoma produces a distinctive thick solid or layered periosteal response distant from the lesion along the diametaphyseal shaft. Observation of this unique periosteal response may help to distinguish chondroblastoma from other epiphyseally centered lesions.

Adolescent↗

Temporal fascial periosteal and musculoperiosteal flaps in the pig: design and blood flow assessment.

The availability of a vascularized periosteal flap with bone-forming potential could greatly enhance the reconstructive capabilities of the craniofacial surgeon. Previous observations seem to indicate that the bone-forming potential of periosteal flaps depends on the vascularity of the flap. The purpose of the present experiment was to design temporal fascial periosteal and musculoperiosteal flaps in the pig and to compare the periosteal blood flow with unoperated periosteum in the same location. The radioactive microsphere (15-micron diameter) technique was used to measure periosteal capillary blood flow in periosteal flaps and unoperated control, randomized to each side of the head in nine pigs (Yorkshire; weight, 12-14 kg). The periosteum was (1) raised based on the temporalis muscle with vascular supply from the deep temporal vessels (n = 6), (2) raised based on temporoparietal fascia-deep temporal fascia with blood supply from the superficial temporal vessels (n = 6), or (3) left intact (n = 6). The mean periosteal capillary blood flow rates in the intact periosteum (0.107 +/- 0.001 ml/min/g), the temporal musculoperiosteal flaps (0.081 +/- 0.01 ml/min/g), and temporal fascial periosteal flaps (0.087 +/- 0.012 ml/min/g) were not significantly different. These observations indicate that the blood flows for both musculoperiosteal and fascial periosteal flaps were comparable to control intact temporal periosteum.

Analysis of Variance↗

Bone fragility: failure of periosteal apposition to compensate for increased endocortical resorption in postmenopausal women.

UNLABELLED: The increase in bone fragility after menopause results from reduced periosteal bone formation and increased endocortical resorption. Women with highest remodeling had greatest loss of bone mass and estimated bone strength, whereas those with low remodeling lost less bone and maintained estimated bone strength. INTRODUCTION: Bone loss from the inner (endocortical) surface contributes to bone fragility, whereas deposition of bone on the outer (periosteal) surface is believed to be an adaptive response to maintain resistance to bending. MATERIALS AND METHODS: To test this hypothesis, changes in bone mass and estimated indices of bone geometry and strength of the one-third distal radius, bone turnover markers, and fracture incidence were measured annually in 821 women 30-89 years of age for 7.1 +/- 2.5 years. The analyses were made in 151 premenopausal women, 33 perimenopausal women, 279 postmenopausal women, and 72 postmenopausal women receiving hormone replacement therapy (HRT). RESULTS: In premenopausal women, periosteal apposition increased the radius width, partly offsetting endocortical resorption; therefore, the estimated cortical thickness decreased. Outward displacement of the thinner cortex maintained bone mass and cortical area and increased estimated bending strength. Estimated endocortical resorption accelerated during perimenopause, whereas periosteal apposition decreased. Further cortical thinning occurred, but estimated bending strength was maintained by modest outward cortical displacement. Endocortical resorption accelerated further during the postmenopausal years, whereas periosteal apposition declined further; cortices thinned, but because outward displacement was minimal, estimated cortical area and bending strength now decreased. Women with highest remodeling had the greatest loss of bone mass and strength. Women with low remodeling lost less bone and maintained estimated bone strength. In HRT-treated women, loss of bone strength was partly prevented. These structural indices predicted incident fractures; a 1 SD lower section modulus doubled fracture risk. CONCLUSIONS: Periosteal apposition does not increase after menopause to compensate for bone loss; it decreases. Bone fragility of osteoporosis is a consequence of reduced periosteal bone formation and increased endocortical resorption. Understanding the mechanisms of the age-related decline in periosteal apposition will identify new therapeutic targets. On the basis of our results, it may be speculated that the stimulation of periosteal apposition will increase bone width and improve skeletal strength.

Adult↗

Periosteal reaction of the ribs in neonates treated with extracorporeal membrane oxygenation: prevalence and association with soft-tissue swelling.

OBJECTIVE: The objectives of the study were to determine the prevalence of periosteal reaction of the ribs in infants treated with extracorporeal membrane oxygenation and to evaluate its association with soft-tissue swelling. MATERIALS AND METHODS: The chest radiographs of 100 consecutive neonates treated with extracorporeal membrane oxygenation were evaluated to determine the maximal soft-tissue swelling during therapy and whether periosteal reaction of the ribs developed. The length of extracorporeal membrane oxygenation and the time elapsed before periosteal reaction developed were recorded. The medical records of those with periosteal reaction were reviewed to determine known causes of this condition. The records of a control group of 11 neonates were evaluated in the same manner. RESULTS: Periosteal reaction of the ribs developed in 13 (21%) of the 61 neonates who had less than 11 mm of soft-tissue swelling. In 69% of those with periosteal reaction, the finding first was seen 21-32 days after birth. In the control group, periosteal reaction developed in only one, a neonate who had vibrator chest physiotherapy. CONCLUSION: Periosteal reaction of the ribs in patients treated with extracorporeal membrane oxygenation is associated with soft-tissue swelling greater than 11 mm. The periosteal reaction appears to be a self-limiting and benign process.

Edema↗

Gross periostitis ossificans in mandibular osteomyelitis. Review of the English literature and radiographic variation.

OBJECTIVE: The purpose of this study was to describe a radiographic variety of gross periostitis ossificans in mandibular osteomyelitis and to determine what types of gross periostitis ossificans are related to a specific form of mandibular osteomyelitis without demonstrable causes. STUDY DESIGN: We reviewed 20 cases of gross periostitis ossificans in patients with mandibular osteomyelitis that had been reported with illustrations in the English literature, and we reviewed our own 14 cases of gross periostitis ossificans, previously reported. The radiographic features of the 34 cases of gross periostitis ossificans were classified according to the status of original contour and the appearance of gross periostitis ossificans. Histopathologic features were studied in 12 cases. RESULTS: The 34 cases of gross periostitis ossificans could be classified radiographically into 4 types. Type A, showing an "onion-skin" appearance, was caused by a carious tooth or followed extraction of a tooth. Type B and type C showed a consolidation form; in the 36.8% (7/19) of these cases in which no infectious source could be identified, it was suspected that the condition was caused by a developing unerupted tooth or a dental follicle. Type D was seen in the most chronic stage. Biopsy specimens of 12 cases commonly showed proliferation of newly formed bone, loose interstitial fibrous tissue, and a low-grade inflammatory cell infiltration. CONCLUSION: Gross periostitis ossificans of type B or type C may be a specific form of mandibular osteomyelitis without demonstrable cause.

Adolescent↗

Prospective study of periostitis and finger clubbing in primary biliary cirrhosis and other forms of chronic liver disease.

The association of finger clubbing and periostitis has been reported in primary biliary cirrhosis and, more rarely, in other forms of chronic liver disease. The prevalence of periostitis and its relationship to finger clubbing is unknown. In this prospective study, we have determined the prevalence of periostitis and finger clubbing in 74 patients with primary biliary cirrhosis and 54 with other forms of chronic liver disease. Clubbing was present in 24% of patients with primary biliary cirrhosis, 29% with HBsAg negative chronic active hepatitis, and 23% in the group of miscellaneous liver diseases. Symmetrical periostitis affecting the tibiae and fibulae occurred in 35% of patients with primary biliary cirrhosis, 29% with chronic, active hepatitis and 40% of patients in the miscellaneous group. The distal radii and ulnae were affected in only eight patients (6%). In primary biliary cirrhosis, the presence of finger clubbing was strongly associated with periostitis (P less than 0.01), but this association was uncommon in other forms of chronic liver disease. In all forms of chronic liver disease periostitis commonly occurs in the absence of finger clubbing. Marked tenderness over the distal leg bones is a reliable sign of underlying periostitis, but this sign is present in only a third of affected patients. This study indicates that periostitis affecting the lower leg bones is common in patients with chronic liver disease, and its presence should be sought whether or not the patient has finger clubbing.

Adult↗

Transverse periosteal sectioning and femur growth in the rat.

Circumferential cuts through the periosteal covering of long bones have been demonstrated to transiently increase epiphyseal growth. This effect appears to be independent of vascular changes accompanying surgery and has been hypothesized to relate to releasing tension in the periosteal envelope. This study was designed to address problems of previous investigations by controlling for the effects of the surgical procedure and by using regression analyses to analyze intra- and interanimal variations in the length and proportionality of the femur in experimental, sham, and control Sprague-Dawley male rat littermates. Experimental animals received circumferential periosteal sectioning of the right femur and no operation to the left limb. A sham operation without periosteal sectioning was performed on the right femur in the sham group. Right to left differences were analyzed using two multiple regression models; one involved three absolute length measurements as the dependent variables, while the other used the three ratios of these length measurements as the dependent variables. The ratio measures were utilized to reflect changes in bone proportionality. Circumferential periosteal section was followed by an alteration in the shape of rat femurs at 2 weeks postsurgery with a slight retardation of the length dimension from medial epicondyle to head of the femur and an overgrowth of the length dimension from the lateral epicondyle to the greater trochanter. The sham procedure produced a proportional decrease in all length measurements. The experimental procedure was also associated with surface bone apposition at the site of section. At 3 weeks postsurgery, normalization of bony contours between sham, experimental, and control groups had occurred; however, there were still some statistically significant decreases of length dimensions in the sham and experimental groups. In the experimental group the length measurement involving the weight-bearing head of the femur remained reduced at 3 weeks postsurgery. It is hypothesized that the functional demands of the long bone play an important role in the effect of periosteal regulation on growth. In situations where a normal tensive force is exerted on the bone, the periosteal envelope will act to restrain epiphyseal growth. When the bone is under a normal compressive force the release of periosteal tension is not a quantitatively significant stimulus to epiphyseal growth and the effects of surgical intervention and muscle trauma will play a more important role in the growth response of the epiphyses.

Animals↗

Induction of cholinergic function in cultured sympathetic neurons by periosteal cells: cellular mechanisms.

Periosteum, the connective tissue surrounding bone, alters the transmitter properties of its sympathetic innervation during development in vivo and after transplantation. Initial noradrenergic properties are downregulated and the innervation acquires cholinergic and peptidergic properties. To elucidate the cellular mechanisms responsible, sympathetic neurons were cultured with primary periosteal cells or osteoblast cell lines. Both primary cells and an immature osteoblast cell line, MC3T3-E1, induced choline acetyltransferase (ChAT) activity. In contrast, lines representing marrow stromal cells or mature osteoblasts did not increase ChAT. Growth of periosteal cells with sympathetic neurons in transwell cultures that prevent direct contact between the neurons and periosteal cells or addition of periosteal cell-conditioned medium to neuron cultures induced ChAT, indicating that periosteal cells release a soluble cholinergic inducing factor. Antibodies against LIFRbeta, a receptor subunit shared by neuropoietic cytokines, prevented ChAT induction in periosteal cell/neuron cocultures, suggesting that a member of this family is responsible. ChAT activity was increased in neurons grown with periosteal cells or conditioned medium from mice lacking either leukemia inhibitory factor (LIF) or LIF and ciliary neurotrophic factor (CNTF). These results provide evidence that periosteal cells influence sympathetic neuron phenotype by releasing a soluble cholinergic factor that is neither LIF nor CNTF but signals via LIFRbeta.

3T3 Cells↗

The enhancement of periosteal chondrogenesis in organ culture by dynamic fluid pressure.

Cartilage repair by autologous periosteal arthroplasty is enhanced by continuous passive motion (CPM) of the joint after transplantation of the periosteal graft. However, the mechanisms by which CPM stimulate chondrogenesis are unknown. Based on the observation that an oscillating intra-synovial pressure fluctuation has been reported to occur during CPM (0.6-10 kPa), it was hypothesized that the oscillating pressure experienced by the periosteal graft as a result of CPM has a beneficial effect on the chondrogenic response of the graft. We have developed an in vitro model with which dynamic fluid pressures (DFP) that mimic those during CPM can be applied to periosteal explants while they are cultured in agarose gel suspension. In this study periosteal explants were treated with or without DFP during suspension culture in agarose, which is conducive to chondrogenesis. Different DFP application times (30 min, 4 h, 24 h/day) and pressure magnitudes (13, 103 kPa or stepwise 13 to 54 to 103 kPa) were compared for their effects on periosteal chondrogenesis. Low levels of DFP (13 kPa at 0.3 Hz) significantly enhanced chondrogenesis over controls (34 +/- 7% vs 14 +/- 5%; P < 0.05), while higher pressures (103 kPa at 0.3 Hz) completely inhibited chondrogenesis, as determined from the percentage of tissue that was determined to be cartilage by histomorphometry. Application of low levels of DFP to periosteal explants also resulted in significantly increased concentrations of Collagen Type II protein (43 +/- 8% vs 10 +/- 5%; P < 0.05). New proteoglycan synthesis, as measured by 35S-sulphate uptake was increased by 30% in periosteal explants stimulated with DFP (350 +/- 50 DPM vs 250 +/- 75 DPM of 35S-sulphate uptake/microg total protein), when compared to controls though this difference was not statistically significant. The DFP effect at low levels was dose-dependant for time of application as well, with 4 h/day stimulation causing significantly higher chondrogenesis than just 30 min/day (34 +/- 7 vs 12 +/- 4% cartilage; P < 0.05) and not significantly less than that obtained with 24 h/day of DFP (48 +/- 9% cartilage, P > 0.05). These observations may partially explain the beneficial effect on cartilage repair by CPM. They also validate an in vitro model permitting studies aimed at elucidating the mechanisms of action of mechanical factors regulating chondrogenesis. The fact that these tissues were successfully cultured in a mechanical environment for six weeks makes it possible to study the actions of mechanical factors on the entire chondrogenic pathway, from induction to maturation. Finally, these data support the theoretical predictions regarding the role of hydrostatic compression in fracture healing.

Animals↗

Clinical Review: Sex steroids and the periosteum--reconsidering the roles of androgens and estrogens in periosteal expansion.

CONTEXT: Traditionally, differences in periosteal bone formation between men and women have been assumed to reflect two diverging endocrine effects: stimulatory effects of androgens in men and inhibitory effects of estrogens in women. In line with this concept, it is tempting to speculate that men experience more periosteal bone expansion than women because they are exposed to more endogenous androgens and less estradiol. However, recent data challenge this traditional concept. EVIDENCE ACQUISITION: A PubMed search was conducted for relevant most recent findings in both humans and animals in the context of an intriguing observation of ongoing periosteal expansion after estrogen treatment in an aromatase-deficient boy. EVIDENCE SYNTHESIS: Human experiments of nature have provided evidence that androgens and estrogens are both required for the process of pubertal periosteal bone expansion typically associated with the male bone phenotype. Androgens alone appear insufficient to drive male periosteal bone formation. In both sexes, androgens may stimulate periosteal bone formation, but low levels of estrogen may increase the mechanical sensitivity of the periosteum. Higher concentrations of endogenous estrogen, however, inhibit periosteal bone apposition and/or its interaction with mechanical loading. This biphasic action of estrogen on the periosteum may result from a direct effect on its receptor, either alpha or beta, but may also depend on changes in serum IGF-I. CONCLUSIONS: Simple concepts of the roles of sex steroids in periosteal apposition have to be reconsidered in the context of these recent findings.

Androgens↗

Periosteal chondrosarcoma: a case report and review of the literature.

Periosteal chondrosarcoma occurs predominantly in the long tubular bones. The long-term survival rate is better and there are fewer local recurrences than with central chondrosarcoma. A case of periosteal chondrosarcoma is reported with a review of the literature. A 13-year-old girl presented with swelling of the distal right thigh of 3 weeks' duration. Radiographs and computed tomographic scan of the lesion showed a soft tissue mass, measuring 6 x 6 cm, with matrix calcification arising from the surface of the bone. An open biopsy followed by en bloc resection of the tumor was performed. The histologic features were those of a chondrosarcoma. An 8-year follow-up period has shown no local recurrence or distant metastases. The differential diagnosis of periosteal chondrosarcoma includes periosteal (chondroblastic) osteosarcoma and periosteal chondroma. Controversy exists as to whether periosteal chondrosarcoma is an entity distinct from periosteal osteosarcoma. The clinicopathologic features in this case and in the cases reported in the literature support the contention that periosteal chondrosarcoma is indeed distinct.

Adolescent↗

Prostaglandin-induced neonatal periostitis.

Prostaglandins are being commonly used to maintain the patency of the ductus arteriosus in infants with congenital ductal-dependent heart disease. A significant and unusual side effect of this drug treatment is the symmetrical development of periostitis of the long bones. A review of neonates with congenital heart disease requiring prostaglandin treatment at the Children's Hospital of Eastern Ontario revealed five infants who developed periostitis, the earliest onset being after 14 days of prostaglandin infusion. The drug dosage varied in these infants from 0.02 to 0.10 micrograms/kg/min. The periostitis was associated with limb pain and considerable swelling of the extremities in all children. The periostitis improved on cessation of the prostaglandin infusion, and by 6 weeks after the cessation of the drug, the periostitis had decreased significantly. Periostitis seemed more dependent on the duration of administration of the prostaglandin than on the dosage of prostaglandin administered. Awareness of this entity is essential not only for the treatment team caring for these infants but also for consultant pediatric orthopaedists to avoid excessive investigation for infection, metabolic disease, or vitamin deficiencies that resemble prostaglandin-induced periostitis.

Ductus Arteriosus, Patent↗

[Periosteal reaction].

The periosteal membrane covers the cortical bone except for the articular surface. The deep layer of the periosteum contains bone-forming mesenchymal cells, capillaries, and nerves. This layer is more active in infants than in adults. Prostaglandin osteopathy, infantile cortical hyperostosis, hypervitaminosis A, and congenital syphilis are examples of periostitis in infants. Incidental asymptomatic periosteal reactions are usually either physiological changes or cortical bone irregularities simulating periostitis. On the other hand, symptomatic periosteal reactions of single bone, such as bone tumor, tumor-like lesion, infection, and trauma, are always pathologic. Careful radiological analysis of periosteal reactions is needed to evaluate the activity and aggressiveness of the lesions. Periosteal reactions of multiple bones usually show solid smooth or undulating patterns. They include pachydermoperiostosis, secondary hypertrophic osteoarthropathy, vascular insufficiency, renal osteodystrophy, and thyroid acropachy. These are usually skeletal manifestations of systemic disorders.

Adult↗

Histochemical evidence of the initial chondrogenesis and osteogenesis in the periosteum of a rib fractured model: implications of osteocyte involvement in periosteal chondrogenesis.

We have examined cellular events at the early stages of periosteal chondrogenesis and osteogenesis induced by bone fracture, using a well-standardized rib fracture model of the mouse. The initial cellular event was recognized as considerable proliferation in the deeper layer referred to as the "cambium layer" of the periosteum, as evidenced by numerous proliferating cell nuclear antigen-positive cells. The periosteal cartilage and bone were then regenerated directly from the region of the most-differentiated cell, i.e., mature osteoblasts of the cambium layer both close to and distant from the fracture site. Therefore, periosteal osteoblasts appeared to have the potential to differentiate into chondrogenic and osteoblastic lineages. CD31-positive blood vessels were uniformly localized along the periosteum that was regenerating cartilage and bone, being therefore indicative of less influence on the initiation of osteochondrogenesis. In contrast, however, the regenerated periosteal cartilage or bone extended from the cortical bones included dead or living osteocytes, respectively. Empty lacunae and lacunae embedded with amorphous materials were found close to the regenerated cartilage, while intact osteocytes persisted adjacent to the regenerated bone. The embedded lacunae with amorphous materials would render the tissue fluid, nutrients, oxygen, and several secretory factors such as dentin matrix protein-1 impossible to be delivered to the periosteal osteoblasts that interconnect osteocytes via gap junctions. Our study thus provides two major clues on initial cellular events in response to bone fracture: the potentiality of periosteal osteoblastic differentiation into a chondrogenic lineage, and a putative involvement of osteocytes in periosteal cartilage and bone regeneration.

Animals↗

Culture-expanded human periosteal-derived cells exhibit osteochondral potential in vivo.

Periosteal cells were enzymatically liberated from human rib periostea obtained from autopsies of 37 donors with an age distribution ranging from 25 weeks of gestation to 88 years old. These cells were introduced into cell culture and subcultured when they reached confluence. After subculture, the adherent periosteal-derived cells showed a nondescript, fibroblast-like morphology in cell culture. The cells from various passages of each donor were tested for in vivo osteochondrogenic potential with three different assay methods in athymic mice: (a) inoculation assay--the cells were directly inoculated into a subcutaneous site, (b) porous ceramics assay--the cells were combined with porous calcium phosphate ceramics, and this composite graft was implanted into a subcutaneous site, and (c) diffusion chamber assay--the cells were loaded into diffusion chambers and cultured in the peritoneal cavity. Frozen-preserved and recultured periosteal-derived cells were also assayed in the same way. In cases of donors younger than 19 years old, cultured, periosteal-derived cells from up to several passages consistently formed bone and/or cartilage in each of the three assays. Frozen-preserved and recultured cells from these donors also formed bone and/or cartilage after introduction into the three in vivo assays. In cases of donors older than 22 years of age, cultured, periosteal-derived cells formed neither bone nor cartilage in vivo. Cultured muscle fibroblasts from some of the same donors did not form bone or cartilage when assayed in vivo under identical conditions. These results suggest that periosteal cells with osteochondrogenic potentials can be liberated from the periosteum of a rib of human donors up to a certain age. Importantly, this potential is retained after enzymatic liberation, cell culture, subculturing, and freeze preservation. The present results suggest that culture-expanded human periosteal-derived cells from young donors may be useful in the repair of skeletal defects to foster cell-mediated regeneration of skeletal tissues, and that this methodology can be used to elucidate cellular, molecular, and genetic disorders in various metabolic bone diseases and skeletal dysplasias.

Adult↗